GLUT4、PPP1Cgamma表达在肝移植围术期胰岛素抵抗中的作用
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摘要
第一部分GLUT4、PPP1Cgamma表达在肝硬化病人胰岛素抵抗中的作用
序言:
肝硬化病人60%～80%可发生糖耐量异常,10%～20%可最终发展为糖尿病。其相关的发生机制尚不清楚,目前认为可能与高胰岛素血症和外周组织的胰岛素抵抗有关。
胰岛素抵抗即指肝脏、骨骼肌、脂肪等组织对胰岛素作用的敏感性下降,胰岛素效应细胞对单位浓度的胰岛素反应减弱。胰岛素在细胞水平的生物作用是通过与靶细胞膜上特异的胰岛素受体(InsR)结合而启动胰岛素一系列信号传导通路,最终使胰岛素敏感组织细胞内葡萄糖转运蛋白4(GLUT4)转位到细胞表面,把细胞外的葡萄糖转运到细胞内,进行糖原的合成、氧化分解,并抑制糖内生等一系列代谢过程,使血糖维持在正常水平。被GLUT4转运到细胞内的葡萄糖主要经1型蛋白磷酸酶(PP1)途径合成糖原,PP1是胰岛素激活糖原合成酶途径中的主要磷酸酶,是由调节亚单位和催化亚单位组成的异二聚体。调节亚单位与骨骼肌糖原有高度亲和力,能正性调节催化亚单位的去磷酸化作用,并激活糖原合成酶并合成糖原。研究认为GLUT4在葡萄糖的吸收和利用上起了关键限速作用,GLUT4的表达下降或转位障碍将引起胰岛素抵抗。由PPP1R3A基因所编码的PP1调节亚单位的缺失也将导致糖原合成酶活性的急剧下降,使得骨骼肌糖原含量减少,并产生胰岛素的抵抗。研究认为肝硬化病人胰岛素抵抗主要表现为葡萄糖的摄取减少和非氧化处置(糖原合成)减少,主要是肌糖原合成功能下降。目前有关GLUT4与肝硬化胰岛素抵抗研究还很少,编码PP1催化亚单位的PPP1Cgamma表达与胰岛素抵抗的研究尚未见报道。
目前在我国接受肝移植手术的患者主要是重症乙肝肝硬化病人。为进一步研究GLUT4、PPP1Cgamma表达在肝移植病人围术期胰岛素抵抗中的作用,我们将首先研究GLUT4、PPP1Cgamma表达在肝硬化病人胰岛素抵抗中的作用。本课题一方面通过检测比较正常人、代偿期肝硬化病人和失代偿期肝硬化病人的空腹血糖、胰岛素、C肽、胰岛素敏感性来研究不同程度肝硬化病人的胰岛素抵抗现象,另一方面通过检测并比较正常人、代偿期肝硬化病人和失代偿期肝硬化病人腹直肌GLUT4、PPP1Cgamma基因及其蛋白表达量,来研究GLUT4、PPP1Cgamma表达在肝硬化胰岛素抵抗中的作用,为临床进一步研究肝移植围术期胰岛素抵抗及肝移植后糖尿病提供基础。
资料与方法:
研究对象分为三组,即正常对照组、肝硬化代偿组和肝硬化失代偿组。正常对照组:活体肝或肾移植供体25例,肝功能Child-Pugh分级均为A级;肝硬化代偿组:乙肝肝硬化作脾脏切除术的患者17例,肝功能Child-Pugh分级均为A级;肝硬化失代偿组:重症乙肝肝硬化作肝移植的患者20例,肝功能Child-Pugh分级C级12例,B级8例。三组研究对象均在麻醉前从桡动脉有创测压管采外周血6ml,用快速血糖仪检测空腹血糖,用化学发光免疫分析法测定空腹胰岛素和C肽。并用计算出胰岛素敏感指数:公式为ln[1/(空腹血糖×空腹胰岛素)]。并在手术进腹时取腹直肌适量,并切成50～100mg数块,用液氮速冻后置于-80℃超低温冰箱中待测。用Western-blot法检测腹直肌GLUT4、PPP1Cgamma蛋白表达量,以real-time PCR方法检测腹直肌PPP1Cgamma mRNA的表达。统计分析所有实验数据经SPSS16.0软件进行统计学处理,p<0.05判定有统计学差异。
结果:
两组肝硬化病人的空腹血糖都明显高于正常组(P<0.01),肝硬化代偿组与肝硬化失代偿组间空腹血糖无明显差异。两组肝硬化病人的空腹血胰岛素水平都明显明显高于正常组(P<0.01),且肝硬化失代偿组的血胰岛素水平也高于肝硬化代偿组,差异有显著性(P<0.05)。两组肝硬化病人的血C-肽水平都明显高于正常组(P<0.01),且肝硬化失代偿组的血C-肽水平也明显高于肝硬化代偿组,有显著差异(P<0.01)。两组肝硬化病人的胰岛素敏感指数都明显低于正常组(P<0.01),肝硬化失代偿组的胰岛素敏感指数虽然低于肝硬化代偿组,但无统计学差异。两组肝硬化组病人骨骼肌GLUT4的蛋白表达量与正常对照组无明显差别,肝硬化失代偿组GLUT4的蛋白表达量与代偿组也无差别。两组肝硬化病人骨骼肌PPP1Cgamma mRNA和蛋白表达量均显著低于正常对照组,差异有非常显著性(P<0.01),两组肝硬化病人组间无明显差别。
结论:
(1)肝硬化病人存在糖代谢异常与胰岛素抵抗;
(2)肝硬化病人的胰岛素抵抗与其骨骼肌GLUT4的表达无明显相关;
(3)肝硬化病人骨骼肌PP1的催化亚单位PPP1Cgamma mRNA和蛋白的含量明显减少,可能是形成肝硬化病人胰岛素抵抗的原因之一。
序言:
肝移植是目前治疗终末期肝病的最有效方法。肝移植手术创伤大、失血多,时间长,术中内环境变化剧烈,严重威胁病人的生命。其中一个重要的内环境变化是病人围术期血糖的升高及严重的胰岛素抵抗现象。肝移植围术期高血糖、胰岛素抵抗可导致患者水、电解质、酸碱平衡的紊乱,甚至出现高渗性昏迷;也是肝移植患者术后出现认知功能障碍的原因之一;更是肝移植术后病人早期感染的危险因子。从长期来看,肝移植手术病人围术期高血糖、胰岛素抵抗现象可发展成肝移植后糖尿病并严重影响肝移植后病人的长期生存。
胰岛素抵抗即指肝脏、骨骼肌及脂肪等组织对胰岛素作用的敏感性下降,胰岛素效应细胞对单位浓度的胰岛素反应减弱。胰岛素在细胞水平的生物作用是通过与靶细胞膜上特异的胰岛素受体结合而启动胰岛素一系列信号转导通路,最终使胰岛素敏感组织细胞内葡萄糖转运蛋白4(GLUT4)转位到细胞表面,GLUT4把细胞外的葡萄糖转运到细胞内,并进行一系列的代谢过程,使血糖维持在正常水平。GLUT-4在葡萄糖的吸收和利用上起了关键限速作用,GLUT-4的表达下降或转位障碍与2型糖尿病和胰岛素抵抗有关。被GLUT4转运到细胞内的葡萄糖主要通过1型蛋白磷酸酶(glycogen-bound Protein phosphatase1,PP1)途径合成糖原。PP1是胰岛素激活糖原合成酶途径中的主要磷酸酶,由催化亚单位和调节亚单位构成。PP1的调节亚单位具有底物特异性,且能正性调节催化亚单位的去磷酸化作用,使糖原合成酶去磷酸化而被激活,并进一步合成糖原。GLUT4在葡萄糖的吸收和利用上起了关键限速作用,GLUT4的表达下降或转位障碍与2型糖尿病和胰岛素抵抗有关。编码PP1调节亚单位的PPP1R3的突变或表达量下调也将严重影响血糖水平并产生胰岛素的抵抗。有关GLUT4和PP1催化亚单位PPP1Cgamma表达变化与肝移植病人胰岛素抵抗的研究还尚未见报道。
目前临床上胰岛素抵抗的研究主要集中在2型糖尿病病人,而有关肝移植病人围术期胰岛素抵抗的研究还很少。尽管国内外学者已对肝移植围术期高血糖、胰岛素抵抗这一现象进行了关注和研究,但主要还是集中在肝移植围术期糖代谢相关激素的研究上,且分歧很大。我们第一部分的研究已经显示肝硬化肝移植的病人在移植前就存在肝硬化相关的胰岛素抵抗及骨骼肌PPP1Cgamma基因及其蛋白表达量的下降,这可能是肝移植病人围术期胰岛素抵抗的原因之一,本课题拟进一步通过比较肝移植前后患者血糖、胰岛素、C肽、胰岛素敏感性来研究肝移植手术对患者胰岛素敏感性的影响,并通过检测比较肝移植手术前后腹直肌GLUT4、PPP1Cgamma基因及其蛋白表达量的变化,来研究肝移植手术对患者GLUT4、PPP1Cgamma表达的影响及其在肝移植围术期胰岛素抵抗中的作用。
资料与方法:
所有研究对象均来自2007年1～12月我院因重症乙肝肝硬化作原位肝移植手术的患者,共20例,其中男性19例,女性1例,年龄为21～60(50.55±13.28)岁,体重为36～95(64.03±11.62)kg,肝功能Child-Pugh分级B级8例,C级12例。在入手术室后麻醉前、门静脉开放后即刻、开放后半小时、1小时、2小时等各时间点从桡动脉有创测压管采患者外周血6ml,用快速血糖仪检测空腹血糖,用化学发光免疫分析法测定空腹胰岛素和C肽。并用计算出胰岛素敏感指数:公式为ln[1/(空腹血糖×空腹胰岛素)]。并在肝移植手术进腹时、在门静脉开放后半小时取腹直肌适量,用Western-blot法检测腹直肌GLUT4、PPP1Cgamma蛋白表达,以real-time PCR方法检测腹直肌PPP1Cgamma mRNA的表达。所有实验数据经SPSS16.0软件进行统计学处理,p<0.05判定有统计学差异。
结果:
1.血标本结果
门静脉开放后各时间点的血糖值均较术前显著升高,且差异有显著性,P值均小于0.01;开放半小时后的各时间点的血糖值均较开放即刻明显升高,差异有显著性,P值均小于0.05;虽然门静脉开放后各时间点的血胰岛素值高于移植前,但均无统计学差异。肝移植术后患者的血C-肽值较术前有下降趋势,但无统计学差异。胰岛素敏感指数在新肝期即刻明显低于术前,P<0.01;开放后半小时和开放后一小时的胰岛素敏感指数均较术前降低,P<0.05。但开放后两小时胰岛素敏感指数虽然也低于移植前,但无统计学差异。其余各组间均无明显差异。
2.骨骼肌组织Western-blot结果
肝移植手术前、后患者骨骼肌GLUT4蛋白表达量无显著差异。肝移植手术前、后患者骨骼肌PPP1Cgamma蛋白表达量也无显著差异。
3.骨骼肌组织Real-time PCR结果:
肝移植手术前、后患者骨骼肌PPP1Cgamma mRNA的表达无明显差别。
结论:
肝移植手术后患者存在较术前更严重的胰岛素抵抗;肝移植手术前后骨骼肌GLUT4、PPP1Cgamma的表达无显著变化;肝移植手术患者围术胰岛素抵抗除与其术前存在的肝硬化相关的胰岛素敏感性下降、PPP1Cgamma表达下降有关外,还与肝移植手术相关的其他因素有关。
PartⅠThe effects of skeletal GLUT4 and PPPlCgamma expression on the insulin resistance in the liver cirrhosis patients
Introduction:
About 60-80%of patients with liver cirrhosis have glucose intolerance and 10-20%can develop diabetes mellitus(GM) eventually.Central hyperinsulinemia and peripheral insulin-resistance are the main explanations for the high prevalence of diabetes in patients with liver cirrhosis.Insulin resistance refers to the lower sensitivity of the insulin target tissue to insulin.Insulin must combine with the insulin receptor on the target cell membrane which can activate a series of signal transduction system,and ultimately make glucose transporter4(GLUT4) translocate to the cell sursace and then GLUT4 transport glucose outside the cell into the target cell.After transported into cells by GLUT4,glucose is mainly transformed to glucogen.Recently,insulin was shown to stimulate a cascade of phosphorylation-dependent kinases which ultimately activate a glycogen-bound subunit of a phosphatase(regulatory subunit of phosphatase-1,PP1) which promotes dephosphorylation GS by the catalytic subunit to synthesize glycogen. Glucose transport,mediated by GLUT4 translocation,is a rate limiting step in glucose metabolism.Lower expression or insufficient translocation of GLUT4 may be one of the reasons of insulin resistance.It is reported that defective expression or the polymorphism of PPP1R3 which encodes the regulatory subunit of PP1 might be related to the insulin resistance because of lower activity of glycogen synthetase.Reports have said that the insulin resistance in the patients with liver cirrhosis manifest mainly a defective insulin-mediated glucose uptake in peripheral tissue,where nonoxidative glucose disposal(glucogen synthesis mainly) seems to be chiefly impaired,however there are few reports about the effects of GLUT4 and PPPlCgamma(the catalytic subunit of PP1) on the insulin resistance in liver cirrhosis patients.
To investigate the effects of GLUT4 and PPP1Cgamma expression on the perioperative insulin resistance in the lever transplantation patients,we should at first study the the effects of GLUT4 and PPP1Cgamma expression on the insulin resistance in liver cirrhosis patients and explore the mechanism of insulin resistance in liver cirrhosis patients who are the main candidates of liver transplantation in our country.So,we would detect and compare the FSB,fast serum insulin,C-peptide,insulin index and skeletal expression of GLUT4,PPP1 gamma between the healthy people and patients with compensated and uncompensated liver cirrhosis.
Material and methods:
25 living-related donors(control group),17 patients with compensated liver cirrhosis who were selected to have splenectomy because of portal hypertention with chronic hepatitis B(group2,Child-Pugh classification A) and 20 patients with uncompensated liver cirrhosis who had the operation of liver transplantation(group3: Child-Pugh classification C 12cases,B 8 cases ) were recruited in our hospital.We detected FSB,serum insulin,C peptide concentration before anesthesia and the skeletal expression of GLUT4 and PPP1Cgamma of the three groups at the beginning of the operations by western-blot and Real-time PCR,meanwhile,we also studied their differences among the groups by statistical ways with SPSS software.
Results:
The level of FSB of the two groups with liver cirrhosis is significantly higher than that of the control group(p<0.01);There is no difference between the two cirrhosis groups(P>0.05).Fasting serum insulin,C peptide concentration with liver cirrhosis is significantly higher than that of control group(P<0.01),moreover,the level of fasting serum insulin,C peptide with uncompensated liver cirrhosis is significantly higher than that of the compensated liver cirrhosis group(p<0.05).The insulin sensitive index of the liver cirrhosis groups is significantly lower than that of the control group.Although The insulin sensitive index of the uncompensated liver cirrhosis group is lower than that of the compensated liver cirrhosis group,the difference is not significant.The expression of GLUT4 exists no difference among the three groups.The expression of PPP1Cgamma in liver cirrhosis groups is significantly lower than that of the control group(p<0.01),however,There was no difference between the two liver cirrhosis groups.
Conclusion:
The patients with liver cirrhosis exist insulin resistance;The skeletal expression of GLUT4 is normal in liver cirrhosis patients,however,the expression of PPPlCgamma in skeletal muscle is significantly lower.Insulin resistance in liver cirrhosis patients probably is related to the negative effect of the lower expression of PPPlCgamma on glycogen synthesis.Insulin resistance in liver cirrhosis patients probably is not related to the amount of GULT4 expression.
PartⅡThe effects of liver transplantation on the insulin resistance and skeletal expression of GLUT4、PPP1Cgamma of the patients
Introduction:
Liver transplantation is the only definitive way of therapy for patients with end-stage liver diseases,however,its operative trauma、stress and the pathophisilogical specialty of the operation can affect homeostasis of the patients.One of the changes of homeostasis is that the patients manifest hyperglycemia and sever insulin resistance during liver transplantation.Perioperative hyperglycemia and insulin resistance can result in electrolyte imbalance,even hyperosmolar coma.They are also the risk factors of post-operative recognition dysfunction and postoperative infection.Perioperative hyperglycemia and insulin resistance of liver transplantation can develop post-transplantation Diabetes eventually which increased the graft and patient morbidity and mortality.
Insulin resistance refers to the lower sensitivity of the insulin target tissue to insulin.Insulin must combine with the insulin receptor on the target cell membrane which can activate a series of signal transduction system,and ultimately make glucose transporter4(GLUT4) translocate to the cell sursace and then GLUT4 transport glucose outside the cell into the target cell.After transported into cells by GLUT4,glucose is mainly transformed to glucogen to maintain glucose homeostasis.Recently,insulin was shown to stimulate a cascade of phosphorylation-dependent kinases which ultimately activate a glycogen-bound subunit of a phosphatase(regulatory subunit of phosphatase-1,PP1) which promotes dephosphorylation GS by the catalytic subunit to synthesize glycogen.Glucose transport,mediated by GLUT4 translocation,is a rate limiting step in glucose metabolism.Lower expression or insufficient translocation of GLUT4 may be one of the reasons of insulin resistance.It is reported that defective expression or the polymorphism of PPP1R3 which encodes the regulatory subunit of PP1 might be related to the insulin resistance because of lower activity of glycogen synthetase.There are few reports about the effects of GLUT4 and PPP1Cgamma(the catalytic subunit of PP1) on the insulin resistance in liver transplantation patients.
At present,the research on insulin resistance is mainly focused on the patients with type 2 Diabetes.Although there are some Controversial reports about the perioperative hyperglycemia and insulin resistance in the liver transplantation patients,they were at the level of glucose metabolism related hormones.Our previous study demonstrated that the liver transplantation patients exist cirrhosis related insulin resistance and lower skeletal expression of PPP1Cgamma before transplantation which may be some of the reasons that cause the perioperative insulin resistance in the liver transplantation patients.We would like to study the effects of liver transplantation operation on the patient's insulin sensitivity and expression of skeletal GLUT4 and PPP1Cgamma by comparing the FSB,serum insulin,C peptide concentration and expression of skeletal GLUT4 and PPP1Cgamma before and after liver transplantation.
Material and methods:
20 patients with uncompensated liver cirrhosis who had the operation of orthotopic liver transplantation(Child-Pugh classification C 12cases,B 8 cases) were recruited in our hospital.We detected FSB,serum insulin,C peptide concentration before anesthesia、after declamping the portal vein 0min、30min、1h and 2h and Insulin index was calculated by the formula of ln[1/(FBS×insulin)].The expression of GLUT4 and PPP1Cgamma in skeletal muscle at the beginning of the operations and 30min after declamping the portal vein was also detected by the way of western-blot and Real-time PCR.The differences were studied between the two groups by statistical ways with SPSS16.0 software.
Result:
The serum glucose concentration after declamping of the portal vein Omin、 30min、1h and 2h was all significantly higher than that before anesthesia(p<0.01).The serum glucose came to the peak 1h and 2h after declamping of the portal vein.Although the level of serum insulin had a trend to higher than that before the operation,there was no statistical difference.To the contrary,the serum c-peptide had a trend to lower than that before the operation,there was no statistical difference.The insulin index was all significantly lower than that before operation.The skeletal Glut4 and PPPlCgamma expression detected by Western-blot and Real-time PCR existed no difference from that before operation.
Conclusion:
The patients with cirrhosis exist more sever insulin resistance after liver transplantation;The skeletal GLUT4 and PPPlCgamma expression detected by Western-blot and Real-time PCR exists no difference from that before transplantation. The perioperative insulin resistance in liver transplantation patients is not only associated with the preexisted insulin resistance,lower expression of skeletal PPP1Cgamma related to cirrhosis,but also the other factors related to the liver transplantation operation.
序言:
肝硬化病人60%～80%可发生糖耐量异常,10%～20%可最终发展为糖尿病。其相关的发生机制尚不清楚,目前认为可能与高胰岛素血症和外周组织的胰岛素抵抗有关。
胰岛素抵抗即指肝脏、骨骼肌、脂肪等组织对胰岛素作用的敏感性下降,胰岛素效应细胞对单位浓度的胰岛素反应减弱。胰岛素在细胞水平的生物作用是通过与靶细胞膜上特异的胰岛素受体(InsR)结合而启动胰岛素一系列信号传导通路,最终使胰岛素敏感组织细胞内葡萄糖转运蛋白4(GLUT4)转位到细胞表面,把细胞外的葡萄糖转运到细胞内,进行糖原的合成、氧化分解,并抑制糖内生等一系列代谢过程,使血糖维持在正常水平。被GLUT4转运到细胞内的葡萄糖主要经1型蛋白磷酸酶(PP1)途径合成糖原,PP1是胰岛素激活糖原合成酶途径中的主要磷酸酶,是由调节亚单位和催化亚单位组成的异二聚体。调节亚单位与骨骼肌糖原有高度亲和力,能正性调节催化亚单位的去磷酸化作用,并激活糖原合成酶并合成糖原。研究认为GLUT4在葡萄糖的吸收和利用上起了关键限速作用,GLUT4的表达下降或转位障碍将引起胰岛素抵抗。由PPP1R3A基因所编码的PP1调节亚单位的缺失也将导致糖原合成酶活性的急剧下降,使得骨骼肌糖原含量减少,并产生胰岛素的抵抗。研究认为肝硬化病人胰岛素抵抗主要表现为葡萄糖的摄取减少和非氧化处置(糖原合成)减少,主要是肌糖原合成功能下降。目前有关GLUT4与肝硬化胰岛素抵抗研究还很少,编码PP1催化亚单位的PPP1Cgamma表达与胰岛素抵抗的研究尚未见报道。
目前在我国接受肝移植手术的患者主要是重症乙肝肝硬化病人。为进一步研究GLUT4、PPP1Cgamma表达在肝移植病人围术期胰岛素抵抗中的作用,我们将首先研究GLUT4、PPP1Cgamma表达在肝硬化病人胰岛素抵抗中的作用。本课题一方面通过检测比较正常人、代偿期肝硬化病人和失代偿期肝硬化病人的空腹血糖、胰岛素、C肽、胰岛素敏感性来研究不同程度肝硬化病人的胰岛素抵抗现象,另一方面通过检测并比较正常人、代偿期肝硬化病人和失代偿期肝硬化病人腹直肌GLUT4、PPP1Cgamma基因及其蛋白表达量,来研究GLUT4、PPP1Cgamma表达在肝硬化胰岛素抵抗中的作用,为临床进一步研究肝移植围术期胰岛素抵抗及肝移植后糖尿病提供基础。
资料与方法:
研究对象分为三组,即正常对照组、肝硬化代偿组和肝硬化失代偿组。正常对照组:活体肝或肾移植供体25例,肝功能Child-Pugh分级均为A级;肝硬化代偿组:乙肝肝硬化作脾脏切除术的患者17例,肝功能Child-Pugh分级均为A级;肝硬化失代偿组:重症乙肝肝硬化作肝移植的患者20例,肝功能Child-Pugh分级C级12例,B级8例。三组研究对象均在麻醉前从桡动脉有创测压管采外周血6ml,用快速血糖仪检测空腹血糖,用化学发光免疫分析法测定空腹胰岛素和C肽。并用计算出胰岛素敏感指数:公式为ln[1/(空腹血糖×空腹胰岛素)]。并在手术进腹时取腹直肌适量,并切成50～100mg数块,用液氮速冻后置于-80℃超低温冰箱中待测。用Western-blot法检测腹直肌GLUT4、PPP1Cgamma蛋白表达量,以real-time PCR方法检测腹直肌PPP1Cgamma mRNA的表达。统计分析所有实验数据经SPSS16.0软件进行统计学处理,p<0.05判定有统计学差异。
结果:
两组肝硬化病人的空腹血糖都明显高于正常组(P<0.01),肝硬化代偿组与肝硬化失代偿组间空腹血糖无明显差异。两组肝硬化病人的空腹血胰岛素水平都明显明显高于正常组(P<0.01),且肝硬化失代偿组的血胰岛素水平也高于肝硬化代偿组,差异有显著性(P<0.05)。两组肝硬化病人的血C-肽水平都明显高于正常组(P<0.01),且肝硬化失代偿组的血C-肽水平也明显高于肝硬化代偿组,有显著差异(P<0.01)。两组肝硬化病人的胰岛素敏感指数都明显低于正常组(P<0.01),肝硬化失代偿组的胰岛素敏感指数虽然低于肝硬化代偿组,但无统计学差异。两组肝硬化组病人骨骼肌GLUT4的蛋白表达量与正常对照组无明显差别,肝硬化失代偿组GLUT4的蛋白表达量与代偿组也无差别。两组肝硬化病人骨骼肌PPP1Cgamma mRNA和蛋白表达量均显著低于正常对照组,差异有非常显著性(P<0.01),两组肝硬化病人组间无明显差别。
结论:
(1)肝硬化病人存在糖代谢异常与胰岛素抵抗;
(2)肝硬化病人的胰岛素抵抗与其骨骼肌GLUT4的表达无明显相关;
(3)肝硬化病人骨骼肌PP1的催化亚单位PPP1Cgamma mRNA和蛋白的含量明显减少,可能是形成肝硬化病人胰岛素抵抗的原因之一。
序言:
肝移植是目前治疗终末期肝病的最有效方法。肝移植手术创伤大、失血多,时间长,术中内环境变化剧烈,严重威胁病人的生命。其中一个重要的内环境变化是病人围术期血糖的升高及严重的胰岛素抵抗现象。肝移植围术期高血糖、胰岛素抵抗可导致患者水、电解质、酸碱平衡的紊乱,甚至出现高渗性昏迷;也是肝移植患者术后出现认知功能障碍的原因之一;更是肝移植术后病人早期感染的危险因子。从长期来看,肝移植手术病人围术期高血糖、胰岛素抵抗现象可发展成肝移植后糖尿病并严重影响肝移植后病人的长期生存。
胰岛素抵抗即指肝脏、骨骼肌及脂肪等组织对胰岛素作用的敏感性下降,胰岛素效应细胞对单位浓度的胰岛素反应减弱。胰岛素在细胞水平的生物作用是通过与靶细胞膜上特异的胰岛素受体结合而启动胰岛素一系列信号转导通路,最终使胰岛素敏感组织细胞内葡萄糖转运蛋白4(GLUT4)转位到细胞表面,GLUT4把细胞外的葡萄糖转运到细胞内,并进行一系列的代谢过程,使血糖维持在正常水平。GLUT-4在葡萄糖的吸收和利用上起了关键限速作用,GLUT-4的表达下降或转位障碍与2型糖尿病和胰岛素抵抗有关。被GLUT4转运到细胞内的葡萄糖主要通过1型蛋白磷酸酶(glycogen-bound Protein phosphatase1,PP1)途径合成糖原。PP1是胰岛素激活糖原合成酶途径中的主要磷酸酶,由催化亚单位和调节亚单位构成。PP1的调节亚单位具有底物特异性,且能正性调节催化亚单位的去磷酸化作用,使糖原合成酶去磷酸化而被激活,并进一步合成糖原。GLUT4在葡萄糖的吸收和利用上起了关键限速作用,GLUT4的表达下降或转位障碍与2型糖尿病和胰岛素抵抗有关。编码PP1调节亚单位的PPP1R3的突变或表达量下调也将严重影响血糖水平并产生胰岛素的抵抗。有关GLUT4和PP1催化亚单位PPP1Cgamma表达变化与肝移植病人胰岛素抵抗的研究还尚未见报道。
目前临床上胰岛素抵抗的研究主要集中在2型糖尿病病人,而有关肝移植病人围术期胰岛素抵抗的研究还很少。尽管国内外学者已对肝移植围术期高血糖、胰岛素抵抗这一现象进行了关注和研究,但主要还是集中在肝移植围术期糖代谢相关激素的研究上,且分歧很大。我们第一部分的研究已经显示肝硬化肝移植的病人在移植前就存在肝硬化相关的胰岛素抵抗及骨骼肌PPP1Cgamma基因及其蛋白表达量的下降,这可能是肝移植病人围术期胰岛素抵抗的原因之一,本课题拟进一步通过比较肝移植前后患者血糖、胰岛素、C肽、胰岛素敏感性来研究肝移植手术对患者胰岛素敏感性的影响,并通过检测比较肝移植手术前后腹直肌GLUT4、PPP1Cgamma基因及其蛋白表达量的变化,来研究肝移植手术对患者GLUT4、PPP1Cgamma表达的影响及其在肝移植围术期胰岛素抵抗中的作用。
资料与方法:
所有研究对象均来自2007年1～12月我院因重症乙肝肝硬化作原位肝移植手术的患者,共20例,其中男性19例,女性1例,年龄为21～60(50.55±13.28)岁,体重为36～95(64.03±11.62)kg,肝功能Child-Pugh分级B级8例,C级12例。在入手术室后麻醉前、门静脉开放后即刻、开放后半小时、1小时、2小时等各时间点从桡动脉有创测压管采患者外周血6ml,用快速血糖仪检测空腹血糖,用化学发光免疫分析法测定空腹胰岛素和C肽。并用计算出胰岛素敏感指数:公式为ln[1/(空腹血糖×空腹胰岛素)]。并在肝移植手术进腹时、在门静脉开放后半小时取腹直肌适量,用Western-blot法检测腹直肌GLUT4、PPP1Cgamma蛋白表达,以real-time PCR方法检测腹直肌PPP1Cgamma mRNA的表达。所有实验数据经SPSS16.0软件进行统计学处理,p<0.05判定有统计学差异。
结果:
1.血标本结果
门静脉开放后各时间点的血糖值均较术前显著升高,且差异有显著性,P值均小于0.01;开放半小时后的各时间点的血糖值均较开放即刻明显升高,差异有显著性,P值均小于0.05;虽然门静脉开放后各时间点的血胰岛素值高于移植前,但均无统计学差异。肝移植术后患者的血C-肽值较术前有下降趋势,但无统计学差异。胰岛素敏感指数在新肝期即刻明显低于术前,P<0.01;开放后半小时和开放后一小时的胰岛素敏感指数均较术前降低,P<0.05。但开放后两小时胰岛素敏感指数虽然也低于移植前,但无统计学差异。其余各组间均无明显差异。
2.骨骼肌组织Western-blot结果
肝移植手术前、后患者骨骼肌GLUT4蛋白表达量无显著差异。肝移植手术前、后患者骨骼肌PPP1Cgamma蛋白表达量也无显著差异。
3.骨骼肌组织Real-time PCR结果:
肝移植手术前、后患者骨骼肌PPP1Cgamma mRNA的表达无明显差别。
结论:
肝移植手术后患者存在较术前更严重的胰岛素抵抗;肝移植手术前后骨骼肌GLUT4、PPP1Cgamma的表达无显著变化;肝移植手术患者围术胰岛素抵抗除与其术前存在的肝硬化相关的胰岛素敏感性下降、PPP1Cgamma表达下降有关外,还与肝移植手术相关的其他因素有关。
PartⅠThe effects of skeletal GLUT4 and PPPlCgamma expression on the insulin resistance in the liver cirrhosis patients
Introduction:
About 60-80%of patients with liver cirrhosis have glucose intolerance and 10-20%can develop diabetes mellitus(GM) eventually.Central hyperinsulinemia and peripheral insulin-resistance are the main explanations for the high prevalence of diabetes in patients with liver cirrhosis.Insulin resistance refers to the lower sensitivity of the insulin target tissue to insulin.Insulin must combine with the insulin receptor on the target cell membrane which can activate a series of signal transduction system,and ultimately make glucose transporter4(GLUT4) translocate to the cell sursace and then GLUT4 transport glucose outside the cell into the target cell.After transported into cells by GLUT4,glucose is mainly transformed to glucogen.Recently,insulin was shown to stimulate a cascade of phosphorylation-dependent kinases which ultimately activate a glycogen-bound subunit of a phosphatase(regulatory subunit of phosphatase-1,PP1) which promotes dephosphorylation GS by the catalytic subunit to synthesize glycogen. Glucose transport,mediated by GLUT4 translocation,is a rate limiting step in glucose metabolism.Lower expression or insufficient translocation of GLUT4 may be one of the reasons of insulin resistance.It is reported that defective expression or the polymorphism of PPP1R3 which encodes the regulatory subunit of PP1 might be related to the insulin resistance because of lower activity of glycogen synthetase.Reports have said that the insulin resistance in the patients with liver cirrhosis manifest mainly a defective insulin-mediated glucose uptake in peripheral tissue,where nonoxidative glucose disposal(glucogen synthesis mainly) seems to be chiefly impaired,however there are few reports about the effects of GLUT4 and PPPlCgamma(the catalytic subunit of PP1) on the insulin resistance in liver cirrhosis patients.
To investigate the effects of GLUT4 and PPP1Cgamma expression on the perioperative insulin resistance in the lever transplantation patients,we should at first study the the effects of GLUT4 and PPP1Cgamma expression on the insulin resistance in liver cirrhosis patients and explore the mechanism of insulin resistance in liver cirrhosis patients who are the main candidates of liver transplantation in our country.So,we would detect and compare the FSB,fast serum insulin,C-peptide,insulin index and skeletal expression of GLUT4,PPP1 gamma between the healthy people and patients with compensated and uncompensated liver cirrhosis.
Material and methods:
25 living-related donors(control group),17 patients with compensated liver cirrhosis who were selected to have splenectomy because of portal hypertention with chronic hepatitis B(group2,Child-Pugh classification A) and 20 patients with uncompensated liver cirrhosis who had the operation of liver transplantation(group3: Child-Pugh classification C 12cases,B 8 cases ) were recruited in our hospital.We detected FSB,serum insulin,C peptide concentration before anesthesia and the skeletal expression of GLUT4 and PPP1Cgamma of the three groups at the beginning of the operations by western-blot and Real-time PCR,meanwhile,we also studied their differences among the groups by statistical ways with SPSS software.
Results:
The level of FSB of the two groups with liver cirrhosis is significantly higher than that of the control group(p<0.01);There is no difference between the two cirrhosis groups(P>0.05).Fasting serum insulin,C peptide concentration with liver cirrhosis is significantly higher than that of control group(P<0.01),moreover,the level of fasting serum insulin,C peptide with uncompensated liver cirrhosis is significantly higher than that of the compensated liver cirrhosis group(p<0.05).The insulin sensitive index of the liver cirrhosis groups is significantly lower than that of the control group.Although The insulin sensitive index of the uncompensated liver cirrhosis group is lower than that of the compensated liver cirrhosis group,the difference is not significant.The expression of GLUT4 exists no difference among the three groups.The expression of PPP1Cgamma in liver cirrhosis groups is significantly lower than that of the control group(p<0.01),however,There was no difference between the two liver cirrhosis groups.
Conclusion:
The patients with liver cirrhosis exist insulin resistance;The skeletal expression of GLUT4 is normal in liver cirrhosis patients,however,the expression of PPPlCgamma in skeletal muscle is significantly lower.Insulin resistance in liver cirrhosis patients probably is related to the negative effect of the lower expression of PPPlCgamma on glycogen synthesis.Insulin resistance in liver cirrhosis patients probably is not related to the amount of GULT4 expression.
PartⅡThe effects of liver transplantation on the insulin resistance and skeletal expression of GLUT4、PPP1Cgamma of the patients
Introduction:
Liver transplantation is the only definitive way of therapy for patients with end-stage liver diseases,however,its operative trauma、stress and the pathophisilogical specialty of the operation can affect homeostasis of the patients.One of the changes of homeostasis is that the patients manifest hyperglycemia and sever insulin resistance during liver transplantation.Perioperative hyperglycemia and insulin resistance can result in electrolyte imbalance,even hyperosmolar coma.They are also the risk factors of post-operative recognition dysfunction and postoperative infection.Perioperative hyperglycemia and insulin resistance of liver transplantation can develop post-transplantation Diabetes eventually which increased the graft and patient morbidity and mortality.
Insulin resistance refers to the lower sensitivity of the insulin target tissue to insulin.Insulin must combine with the insulin receptor on the target cell membrane which can activate a series of signal transduction system,and ultimately make glucose transporter4(GLUT4) translocate to the cell sursace and then GLUT4 transport glucose outside the cell into the target cell.After transported into cells by GLUT4,glucose is mainly transformed to glucogen to maintain glucose homeostasis.Recently,insulin was shown to stimulate a cascade of phosphorylation-dependent kinases which ultimately activate a glycogen-bound subunit of a phosphatase(regulatory subunit of phosphatase-1,PP1) which promotes dephosphorylation GS by the catalytic subunit to synthesize glycogen.Glucose transport,mediated by GLUT4 translocation,is a rate limiting step in glucose metabolism.Lower expression or insufficient translocation of GLUT4 may be one of the reasons of insulin resistance.It is reported that defective expression or the polymorphism of PPP1R3 which encodes the regulatory subunit of PP1 might be related to the insulin resistance because of lower activity of glycogen synthetase.There are few reports about the effects of GLUT4 and PPP1Cgamma(the catalytic subunit of PP1) on the insulin resistance in liver transplantation patients.
At present,the research on insulin resistance is mainly focused on the patients with type 2 Diabetes.Although there are some Controversial reports about the perioperative hyperglycemia and insulin resistance in the liver transplantation patients,they were at the level of glucose metabolism related hormones.Our previous study demonstrated that the liver transplantation patients exist cirrhosis related insulin resistance and lower skeletal expression of PPP1Cgamma before transplantation which may be some of the reasons that cause the perioperative insulin resistance in the liver transplantation patients.We would like to study the effects of liver transplantation operation on the patient's insulin sensitivity and expression of skeletal GLUT4 and PPP1Cgamma by comparing the FSB,serum insulin,C peptide concentration and expression of skeletal GLUT4 and PPP1Cgamma before and after liver transplantation.
Material and methods:
20 patients with uncompensated liver cirrhosis who had the operation of orthotopic liver transplantation(Child-Pugh classification C 12cases,B 8 cases) were recruited in our hospital.We detected FSB,serum insulin,C peptide concentration before anesthesia、after declamping the portal vein 0min、30min、1h and 2h and Insulin index was calculated by the formula of ln[1/(FBS×insulin)].The expression of GLUT4 and PPP1Cgamma in skeletal muscle at the beginning of the operations and 30min after declamping the portal vein was also detected by the way of western-blot and Real-time PCR.The differences were studied between the two groups by statistical ways with SPSS16.0 software.
Result:
The serum glucose concentration after declamping of the portal vein Omin、 30min、1h and 2h was all significantly higher than that before anesthesia(p<0.01).The serum glucose came to the peak 1h and 2h after declamping of the portal vein.Although the level of serum insulin had a trend to higher than that before the operation,there was no statistical difference.To the contrary,the serum c-peptide had a trend to lower than that before the operation,there was no statistical difference.The insulin index was all significantly lower than that before operation.The skeletal Glut4 and PPPlCgamma expression detected by Western-blot and Real-time PCR existed no difference from that before operation.
Conclusion:
The patients with cirrhosis exist more sever insulin resistance after liver transplantation;The skeletal GLUT4 and PPPlCgamma expression detected by Western-blot and Real-time PCR exists no difference from that before transplantation. The perioperative insulin resistance in liver transplantation patients is not only associated with the preexisted insulin resistance,lower expression of skeletal PPP1Cgamma related to cirrhosis,but also the other factors related to the liver transplantation operation.
引文
[1]Perseghin G,Caloni M,Mazzaferro V,Luzi L.Hepatogenic diabetes Recenti Prog Med,2001 Dec;92(12):757-61.
[2]Bugianesi E,McCullough AJ,Marchesini G:Insulin resistance:a metabolic pathway to chronic liver disease.Hepatology,2005;42:987-1000,
[3]Buyse S,Valla D.Carbohydrate metabolism dysregulation in cirrhosis:pathophysiology,prognostic impact and therapeutic implications.Gastroenterol Clin Biol,2007 Mar;31(3):266-73.
[4]Perseghin G,Mazzaferro V,Sereni LP,et al.Contribution of reduced insulin sensitivity and secretion to the pathogenesis of hepatogenous diabetes:effect of liver transplantation.Hepatology,2000 Mar;31(3):694-703.
[5]Mastsumoto D,Yamanaka-Okumura H,et al.Nutritional treatment of a patient with hepatic cirrhosis with the novel low glycemic index liquid food(Inslow).J Med Invest,2007 Aug;54(3-4):375-80.
[6]Lincano JM,Alessi DR.The Insulin Signalling Pathway.Curr.Biol,2002;12(7):R236-238
[7]Asano T,Fujishiro M,Kushiyama A,et al.Role of phosphatidylinositol 3-kinase activation on insulin action and its alteration in diabetic conditions.Biol Pharm Bull,2007 Sep;30(9):1610-6.
[8]Furtado LM,Somwar R,Sweeney G,et al.Activation of the glucose transporter GLUT4 by insulin.Biochem Cell Biol,2002;80(5):569-78.
[9]Wallberg-Henriksson H,Zierath JR.GLUT4:a key player regulating glucose homeostasis? Insights from transgenic and knockout mice(review).Mol Membr Biol,2001 Jul-Sep;18(3):205-11.
[10]Chang L,Chiang SH,Saltiel AR.Insulin signaling and the regulation of glucose transport.Mol Med,2004 Jul-Dec;10(7-12):65-71
[11]Asano T,Fujishiro M,Kushiyama A,ET AL.Role of phosphatidylinositol 3-kinase activation on insulin action and its alteration in diabetic conditions.Biol Pharm Bull,2007 Sep;30(9):1610-6.
[12]Mott DM,Kida Y,Nyomba BL.Human skeletal muscle type-1 protein phosphatase and insulin resistance.Adv.prot.phosph,1993,7(11):413-417
[13]Ericsson A,Hamark B,Powell TL,et al.Glucose transporter isoform 4 is expressed in the syncytiotrophoblast of first trimester human placenta.Hum Reprod,2005,20:521-30.
[14]Garvey WT,Maianu L,Hancock JA,et,al.Gene expression of GLUT4 in skeletal muscle from insulin resistant patients with obesity,IGT,GDM,and NIDDM.Diabetes,1992;41:465-475.
[15]Pedersen O,Bak JF,Andersen PH,et al.Evidence against altered expression of GLUT1 or GLUT4 in skeletal muscle of patients with obesity or NIDDM.Diabetes,1990;39:865-870.
[16]Mirela D,Christopher GA,Lorraine D.Disruption of the Striated Muscle Glycogen Targeting Subunit PPP1R3A of Protein Phosphatase 1 Leads to Increased Weight Gain,Fat Deposition,and Development of Insulin Resistance.Diabetes,2003,52(3):596-604
[17]David B Savage,Lanmin Zhai,Balasubramanian Ravikumar,et al.A Prevalent Variant in PPP1R3A Impairs Glycogen Synthesis and Reduces Muscle Glycogen Content in Humans and Mice.Mol Cell Endocrinol,2008 Mar 26;285(1-2):10-8.
[18]James X,Clifton B,Michal P.A Type 2 Diabetes-Associated Polymorphic ARE Motif Affecting Expression of PPP1R3 Is Involved in RNA-Protein Interactions.Molecular Genetics and Metabolism,1999,68(6):48-55
[19]Riggio O,Merli M,Leonetti F,et al.Impaired nonoxidative glucose metabolism in patients with liver cirrhosis:effects of two insulin doses.Metabolism,1997 Jul;46(7):840-3.
[20]Kruszynska Y,Williams N,Perry M,Home P.The relationship between insulin sensitivity and skeletal muscle enzyme activities in hepatic cirrhosis.Hepatology,1988 Nov-Dec;8(6):1615-9.
[21]Schneiter P,Gillet M,Chioléro R,et al.Hepatic nonoxidative disposal of an oral glucose meal in patients with liver cirrhosis.Metabolism.1999 Oct;48(10):1260-6
[22]Shmueli E,Walker M,Alberti G,Record CO.Hepatology.Normal splanchnic but impaired peripheral insulin-stimulated glucose uptake in cirrhosis,1993 Jul;18(1):86-95.
[23]Karnieli E,Armoni M.Transcriptional regulation of the insulin- responsive glucose transporter GLUT4 gene:from physiology to pathology.Am J Physiol Endocrinol Metab,2008 Jul;295(1):E38-45.
[24]张霞,沈鼎明.肝源性糖尿病的研究进展.中华肝脏病杂志,2002;10(6):476-8
[25]Kuriyama S,Miwa Y,Fukushima H,et al.Prevalence of diabetes and incidence of angiopathy in patients with chronic viral liver disease.J Clin Biochem Nutr,2007 Mar;40(2):116-22.
[26]Postic C,Girard J.Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance:lessons from genetically engineered mice.J Clin Invest,2008 Mar;118(3):829-38.
[27]施红梅,孟祥伟.肝源性糖尿病发病机制的研究进展.吉林医学,2007;28(2):178-9.
[28]Nikoulina SE,Ciaraldi TP,Abrams-Carter L,et al.Regulation of glycogen synthase activity in cultured skeletal muscle cells from subjects with type Ⅱdiabetes:role of chronic hyperinsulinemia and hyperglycemia.Diabetes,1997 Jun;46(6):1017-24.
[29]Zhang Y,Guan L,Wang X,et al.Protection of chlorophyllin against oxidative damage by inducing HO-1 and NQO1 expression mediated by PI3K/Akt and Nrf2.Free Radic Res,2008 Apr;42(4):362-71.
[30]Elisabeth S,Daniel B,Joan C,et al.A Novel Role of Neuregulin in Skelet al Muscle.The Journal of Biological Chemistry,2001,276(21):18257-18264.
[31]Watson R T,Pessin J.Intracelular organization of insulin signaling and GLUT4 translocation.Recent Prog Horm Res,2001(7),56:175-193.
[32]Holland-Fischer P,Anderson PH,Lund S,et al.Muscle GLUT4 in cirrhosis.J Hepatol,2007,47:212-219.
[33]Maureen J,Charron S,Ellen B,et al.GLUT4 gene regulation and manipulation.Biol Chem,1999,274:3253-3256.
[34]Jessen N,Buhl ES,Schmitz O,et,al.Impaired insulin action despite upregulation of proximal insulin signaling:novel insights into skelet al muscle insulin resistance in liver cirrhosis.J Hepatol,2006 Dec;45(6):797-804.
[35]Kelley DE,Mintun MA,Watkins SC,et al.The effect of non-insulin-dependent diabetes mellitus and obesity on glucose transport and phosphorylation in skelet al muscle.J Clin Invest,1996 Jun 15;97(12):2705-13.
[36]Ryder J W,Yang J,Galuska D,et al.Use of a novel impermeable biotinylated photolabeling reagent to assess insulin-and hypoxia-stimulated cell surface GLUT4 content in skelet al muscle from type 2 diabetic patients.Diabetes,2000,49:647-654.
[37]Nielsen MF,Caumo A,Aagaard NC,et al.Contribution of defects in glucose uptake to carbohydrate intolerance in liver cirrhosis:assessment during physiologic glucose and insulin concentrations.Am J Physiol Gastrointest Liver Physiol,2005,32:34-39
[38]Doney AS,Fischer B,Cecil JE,et al.Male preponderance in early diagnosed type 2 diabetes is associated with the ARE insertion/deletion polymorphism in the PPPlR3Alocus.BMC Genet,2003,4:11.
[39]Mammarella S,Creati B,Staniscia T,et al.Obesity modifies the effects of the Asp905Tyr variant of PPP1R3A on risk of type 2 diabetes and insulin sensitivity.Diabetes Obes Metab,2007 Sep,9(5):759-61.
[40]Bak JF.Insulin receptor function and glycogen synthase activity in human skelet al muscle.Physiology and pathophysiology.Dan Med Bull,1994 Apr,41(2):179-92.
[41]Kakizaki S,Sohara N,Yamazaki Y,et al.Elevated plasma resistin concentrations in patients with liver cirrhosis.J Gastroenterol Hepatol,2008 Jan,23(1):73-77
[42]Kraegen EW,Cooney GJ.Free fatty acids and skelet al muscle insulin resistance.Curr Opin Lipidol,2008 Jun,19(3):235-41.
[43]Griffin ME,Mareueei MJ,Cline GW,et al.Free fatty acid induced insulin resistance is associated with activation of protein kinase C theta and alterations in the insulin signaling cascade.Diabetes,1999,48(6):1270-1274.
[44]Ruddock MW,Stein A,Landaker E,et al.Saturated fatty acids inhibit hepatic insulin action by modulating insulin receptor expression and post-receptor signalling.J Biochem,2008 Nov,144(5):599-607.
[45]Seirafi M,Negro F.Hepatitis C and insulin resistance.Rev Med Suisse,2008,4(169):1859-62.
[46]Aytug S,Reich D,Sapiro LE,et al.Impaired IRS-1/PI3-kinase signaling in patients with HCV:a mechanism for increased prevalence of type 2 diabetes.Hepatology,2003 Dec,38(6):1384-92.
[47]Ryder JW,Gilbert M,Zierath JR.Skelet al muscle and insulin sensitivity:pathophysiological alterations.Front Biosci,2001,6:D154-63.
[1]Grocott HR Hyperglycemia and postoperative cognitive dysfunction:another call for better glycemic control?Can J Anaesth,2008 Mar,55(3):140-5.
[2]Jones R Perioperative glycemic control and postoperative cognitive dysfunction:an expression of caution.Can J Anaesth,2008 Aug,55(8):559-60;
[3]Ammori JB,Sigakis M,Englesbe MJ,et al.Effect of intraoperative hyperglycemia during liver transplantation.J Surg Res,2007 Jun,140(2):227-33.
[4]Saliba F,Lakehal M,Pageaux GP,et al.Risk factors for new-onset diabetes mellitus following liver transplantation and impact of hepatitis C infection:an observational multicenter study.Liver Transpl,2007,13(1):5-7.
[5]Bianchi G,Marchesini G,Marzocchi R,Metabolic syndrome in liver transplantation:relation to etiology and immunosuppression.Liver Transpl,2008 Nov,14(11):1648-54
[6]Cooper ME,Tikellis C,Thomas MC:Preventing diabetes in patients with hypertension:One more reason to block the renin-angiotensin system.J Hypertens Suppl,2006,24:S57-S63
[7]Shinozaki K,Ayajiki K,Nishio Y,et al.Evidence for a causal role of the renin-angiotensin system in vascular dysfunction associated with insulin resistance.Hypertension,2004,43:255-262
[8]Bloom RD,Crutchlow MF.Transplant-associated hyperglycemia.Transplant Rev(Orlando).2008 Jan,22(1):39-51.
[9]Marie Laryea,Kymberly D.Watt,Michele Molinari,et,al.Metabolic Syndrome in Liver Transplant Recipients:Prevalence and Association With Major Vascular Events.LIVER TRANSPLANTATION,2007,13:1109-1114
[10]DeWolf AM,Kang YG,Todo S,Kam I,et al.Glucose metabolism during liver transplantation in dogs.Anesth Analg,1987,66(1):76-80.
[11]Ichimiya M,Takada Y,Shimahara Y,et al.Insulin and glucagon levels in living related liver transplantation:their interaction with the recovery of graft liver function.Transpl Int,1995,8(3):165-168.
[12]Perseghin G,Regalia E,Battezzati A,et al.Regulation of glucose homeosta tasis in humans with denervated livers.J Clin Invest,1997,100(4):931-941.
[13]Shangraw RE,Hexem JG.Glucose and potassium metabolic responses to insulin during liver transplantation.Liver Transpl Surg,1996,2(6):443-454.
[14]Thorell A,Nygren J,Ljungqvist O.Insulin resistance:a marker of surgical stress.Curr Opin Clin Nutr Metab Care,1999 Jan,2(1):69-78.
[15]Soop M,Nygren J,Thorell A,et al.Stress-induced insulin resistance:recent developments.Curr Opin Clin Nutr Metab Care,2007 Mar,10(2):181-6.
[16]Asano T,Fujishiro M,Kushiyama A,et al.Role of phosphatidylinositol 3-kinase activation on insulin action and its alteration in diabetic conditions.Biol Pharm Bull,2007 Sep,30(9):1610-6.
[17]Furtado LM,Somwar R,Sweeney G,et al.Activation of the glucose transporter GLUT4 by insulin.Biochem Cell Biol,2002,80(5):569-78.
[18]Thirone AC,Carvalheira JB,Hirata AE,et al.Regulation of Cbl-associated protein/Cb1 pathway in muscle and adipose tissues of two animal models of insulin resistance.Endocrinology,2004 Jan,145(1):281-93.
[19]Chang L,Chiang SH,Saltiel AR.Insulin signaling and the regulation of glucose transport.Mol Med,2004 Jul-Dec,10(7-12):65-71
[20]Pedersen O,Bak JF,Andersen PH,et al.Evidence against altered expression of GLUT1 or GLUT4 in skelet al muscle of patients with obesity or NIDDM.Diabetes,1990,39:865-870.
[21]Ericsson A,Hamark B,Powell TL,et al.Glucose transporter isoform 4 is expressed in the syncytiotrophoblast of first trimester human placenta.Hum Reprod,2005,20:521-30.
[22]Garvey WT,Maianu L,Hancock JA,et,al.Gene expression of GLUT4 in skeletal muscle from insulin resistant patients with obesity,IGT,GDM,and NIDDM.Diabetes,1992,41:465-475.
[23]Mott DM,Kida Y,Nyomba BL.Human skeletal muscle type-1 protein phosphatase and insulin resistance.Adv.prot.phosph,1993,7(11):413-417.
[24]Mirela D,Christopher GA,Lorraine D.Disruption of the Striated Muscle Glycogen Targeting Subunit PPP1R3A of Protein Phosphatase 1 Leads to Increased Weight Gain,Fat Deposition,and Development of Insulin Resistance.Diabetes,2003,52(3):596-604.
[25]David B Savage,Lanmin Zhai,Balasubramanian Ravikumar,et al.A Prevalent Variant in PPP1R3A Impairs Glycogen Synthesis and Reduces Muscle Glycogen Content in Humans and Mice.Mol Cell Endocrinol,2008 Mar 26,285(1-2):10-8.
[26]Malecki MT.Genetics of type 2 diabetes mellitus.Diabetes Res Clin Pract,2005Jun,68 Suppll:S10-21.
[27]Buyse S,Valla D.Carbohydrate metabolism dysregulation in cirrhosis:pathophysiology,prognostic impact and therapeutic implications.Gastroenterol Clin Biol,2007 Mar,31(3):266-73.
[28]Perseghin G,Mazzaferro V,Sereni LP,et al.Contribution of reduced insulin sensitivity and secretion to the pathogenesis of hepatogenous diabetes:effect of liver transplantation.Hepatology,2000 Mar,31(3):694-703.
[29]施红梅,孟祥伟.肝源性糖尿病发病机制的研究进展.吉林医学,2007,28(2):178-179.
[30]Perseghin G,Mazzaferro V,Sereni LP,et al.COntrmutiOn of reduced insulin sensitivity and secretion to the pathogenesis of hepatogenous diabetes:effect of liver transplantation.Hepatology,2000,31:694-703.
[31]Schneiter P,Gillet M,Chioléro R,et al.Mechanisms of postprandial hyperglycemia in liver transplant recipients:comparison of liver transplant patients with kidney transplant patients and healthy controls.Diabetes Metab,2000 Feb,26(1):51-6.
[32]Riggio O,Merli M,Leonetti F,et al.Impaired nonoxidative glucose metabolism in patients with liver cirrhosis:effects of two insulin doses.Metabolism,1997Jul,46(7):840-3.
[33]Shmueli E,Walker M,Alberti G,Record CO.Hepatology.Normal splanchnic but impaired peripheral insulin-stimulated glucose uptake in cirrhosis,1993 Jul,18(1):86-95.
[34]Kruszynska Y,Williams N,Perry M,Home P.The relationship between insulin sensitivity and skeletal muscle enzyme activities in hepatic cirrhosis.Hepatology,1988 Nov-Dec,8(6):1615-9.
[35]Schneiter P,Gillet M,Chioléro R,et al.Hepatic nonoxidative disposal of an oral glucose meal in patients with liver cirrhosis.Metabolism,1999 Oct,48(10):1260-6
[36]Tietge UJ,Selberg O,Kreter A,et al.Alterations in glucose metabolism associated with liver cirrhosis persist in the clinically stable long-term course after liver transplantation.Liver Transpl,2004 Aug,10(8):1030-40.
[37]Xue C,Aspelund G,Sritharan KC,et al.Isolated hepatic cholinergic denervation impairs glucose and glycogen metabolism.J Surg Res,2000 May 1,90(l):19-25.
[38]Latour MG,Lautt WW.Auton Neurosci.The hepatic vagus nerve in the control of insulin sensitivity in the rat,2002 Jan 10,95(1-2):125-30.
[39]Matsuhisa M,Yamasaki Y,Shiba Y,et al.Important role of the hepatic vagus nerve in glucose uptake and production by the liver.Metabolism,2000 Jan,49(1):11-6.
[40]Dicostanzo CA,Dardevet DP,Neal DW,et al.Role of the hepatic sympathetic nerves in the regulation of net hepatic glucose uptake and the mediation of the portal glucose signal.Am J Physiol Endocrinol Metab,2006 Jan,290(l):E9-E16.
[41]王丽静,刘礼斌.糖皮质激素诱导胰岛素抵抗的分子机制.国际内分泌代谢 杂志,2007,27(6):415-417
[42]Liu C,Wang X,Chen Z,Zhang L,Wu Y,Zhang Y.Hepatic ischemia-reperfusion induces insulin resistance via down-regulation during the early steps in insulin signaling in rats.Transplant Proc,2008 Dec,40(10):3330-4.
[43]Ogawa W,Kasuga M.Insulin signaling and pathophysiology of type 2 diabetes mellitus.Nippon Rinsho,2006 Jul,64(7):1381-9.
[1]Mora PF.Post-transplantation diabetes mellitus.Am J Med Sci,2005 Feb,329(2):86-94.
[2]Saliba F,Lakehal M,Pageaux GP,et al.Risk factors for new-onset diabetes mellitus following liver transplantation and impact of hepatitis C infection:an observational multicenter study.Liver Transpl,2007,13(l):5-7.
[3]Bianchi G,Marchesini G,Marzocchi R,et al.Metabolic syndrome in liver transplantation:relation to etiology and immunosuppression.Liver Transpl,2008Nov,14(11):1648-54.
[4]Bloom RD,Crutchlow MF.Transplant-associated hyperglycemia.Transplant Rev (Orlando),2008 Jan,22(1):39-51.
[5]Grocott HP.Hyperglycemia and postoperative cognitive dysfunction:another call for better glycemic control? Can J Anaesth,2008 Mar,55(3):140-5.
[6]Jones P.Perioperative glycemic control and postoperative cognitive dysfunction:an expression of caution.Can J Anaesth,2008 Aug,55(8):559-60.
[7]Cooper ME,Tikellis C,Thomas MC:Preventing diabetes in patients with hypertension:One more reason to block the renin-angiotensin system.J Hypertens Suppl,2006,24:S57-S63.
[8]Shinozaki K,Ayajiki K,Nishio Y,et al.Evidence for a causal role of the renin-angiotensin system in vascular dysfunction associated with insulin resistance.Hypertension,2004,43:255-262.
[9]Marie Laryea,Kymberly D.Watt,Michele Molinari,et,al.Metabolic Syndrome in Liver Transplant Recipients:Prevalence and Association With Major Vascular Events.LIVER TRANSPLANTATION,2007,13:1109-1114.
[10]余自成,张可蹭.移植后新发生糖尿病治疗和管理指南.世界临床药物,2006,26(9):518-522.
[11]Rabkin JM,Corless CL,Rosen HR,et al.Imnmnosuppression impact on lang-term cardiovascular complications after liver transplantation.Am J Surg,2002,183(5):595-599.
[12]陈琳,盛正妍,王煜非.移植后糖尿病的危险因素及其发病机制的研究进展.中华全科医师杂志,2007,6(3):160-162.
[13]张霞,沈鼎明.肝源性糖尿病的研究进展.中华肝脏病杂志,2002,10(6):476-478.
[14]施红梅,孟祥伟.肝源性糖尿病发病机制的研究进展.吉林医学,2007,28(2):178-180.
[15]Depczynski B,Daly B,Campbell LV,et al.Predicting the occurrence of diabetes mellitus in recipients of heart transplants.Diabet Med,2000 Jan,17(1):15-9.
[16]Hakan K.R.Karlsson,Maria Ahlse'n,Juleen R.Zierath,et al.Insulin Signaling and Glucose Transport in Skeletal Muscle From First-Degree Relatives of Type 2Diabetic Patients.DIABETES,VOL.55,MAY 2006:1283-1288.
[17]Hoban R,Gielda B,Temkit M,et al.Utility of HbA1c in the detection of subclinical post renal transplant diabetes.Transplantation,2006 Feb 15,81(3):379-83.
[18]Torres-Romero LF,Santiago-Delpin EA,de Echegaray S,et al.HLA is not predictive of posttransplant diabetes mellitus.Transplant Proc,2006 Apr,38(3):914-5.
[19]Steinmüller TH,Stockmann M,Bechstein WO,et al.Liver transplantation and diabetes mellitus.Exp Clin Endocrinol Diabetes.2000;108(6):401-5.
[20]Delgado-Borrego A,Casson D,Sehoenfeld D,et al.Hepatitis C virus is independently associated with increased insulin resistance after liver transplantation.Transplantation,2005,77(5):703-710.
[21]Masini M,Campani D,Boggi U,et al.Hepatitis C virus infection and human pancreatic beta-cell dysfunction.Diabetes Care,2005,28(4):940-941.
[22]Neylan JF.Racial differences in renal transplantation after immunosuppression with tacrolimus versus cyclosporine.FK506 Kidney Transplant Study Group.Transplantation,1998 Feb 27,65(4):515-23.
[23]Walczak D,Calvert D,Oberholzer J,et al.Effect of race on the occurrence of posttransplant diabetes in kidney transplant recipients treated with early steroid discontinuation.Transplant Proc,2005 Mar,37(2):819-21
[24]Baltar J,Ortega T,Ortega F,et al.Posttransplantation diabetes mellitus:prevalence and risk factors.Transplant Proc,2005 Nov,37(9):3817-8.
[25]冉兴无.FK506与器官移植术后糖尿病.国外医学泌尿系统分册,2005,25(4):566-568
[26]Campise M.Post-transplant diabetes mellitus:diagnosis and treatment.G Ital Nefrol,2007 Nov-Dec,24 6):547-57.
[27]王丽静,刘礼斌.糖皮质激素诱导胰岛素抵抗的分子机制.国际内分泌代谢杂志,2007,27(6):415-417.
[28]李新,袁莉.移植后糖尿病研究进展,国际移植.血液净化杂志,2006,4(1):38-40.
[29]Midtvedt K,Hjelmesaeth J,Hartmann A,et al.Insulin resistance after renal transplantation:the effect of steroid dose reduction and withdrawal.J Am Soc Nephrol,2004 Dec,15(12):3233-9.
[30]Burroughs TE,Lentine KL,Takemoto SK,et al.Influence of early posttransplantation prednisone and calcineurin inhibitor dosages on the incidence of new-onset diabetes.Clin J Am Soc Nephrol,2007,2(3):517-23.
[31]Rabkin JM,Corless CL,Rosen HR,et al.Immunosuppression impact on long-term cardiovascular complications after liver transplantation.Am J Surg,2002,183(5):595-9.
[32]32:Redmon JB,Olson LK,Armstrong MB,et al.Effects of tacrolimus(FK506)on human insulin gene expression,insulin mRNA levels,and insulin secretion in HIT-T15 cells.J Clin Invest,1996,15,98(12):2786-93.
[33]鞠卫强,何晓顺.肝移植术后代谢并发症.中华肝胆外科杂志,2003,9(5):315-317.
[34]Stockmann M,Konrad T,Nolting S,et al.Major influence of liver function itself but not of immunosuppression determines glucose tolerance after living-donor liver transplantation.Liver Transpl,2006 Apr,12(4):535-543.
[35]Tappy L,Schneiter P,Chiolero R,et al.Effects of a glucose meal on energy metabolism in patients with cirrhosis before and after liver transplantation.Arch Surg,2001 Jan,136(1):80-4.
[36]Colle Ⅰ,Van Vlierberghe H,Troisi R,et al.Transplanted liver:consequences of denervation for liver functions.Anat Rec A Discov Mol Cell Evol Biol,2004 Sep,280(1):924-31.
[37]Kissler HJ,Hauffen J,Hennig R,et al.Glucose and lipid metabolism after liver transplantation in inbred rats:consequences of hepatic denervation.Metabolism,2005 Jul,54(7):881-90.
[38]Schneiter P,Gillet M,Chiolero R,et al.Mechanisms of postprandial hyperglycemia in liver transplant recipients:comparison of liver transplant patients with kidney transplant patients and healthy controls.Diabetes Metab,2000 Feb,26(1):51-6.
[39]39.Schneiter P,Gillet M,Chiolero R,et al.Postprandial hepatic glycogen synthesis in liver transplant recipients.Transplantation,2000 Mar 15,69(5):978-81
[1]Sophie S.Anaesthesia for the elderly patient.J Pak Med Assoc,2007 Apr,57(4):196-201.
[2]Bekker AY,Weeks EJ.Cognitive function after anaesthesia in the elderly.Best Pract Res Clin Anaesthesiol,2003 Jun,17(2):259-72.
[3]Dodds C,Allison J.Postoperative cognitive deficit in the elderly surgical patient.Br J Anaesth,1998 Sep,81(3):449-62.
[4]姚立农,张宏.老年人术后认知功能障碍的研究现状.国外医学麻醉与复苏分册,200 1,22(4):217-220.
[5]Laalou FZ,Carre AC,Forestier C,et al.Pathophysiology of post-operative cognitive dysfunction:current hypotheses.J Chir(Paris),2008 Jul-Aug,145(4):323-30.
[6]Moller JT,Cluitmans P,Rasmussen LS,et al.Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study.ISPOCD investigators.International Study of Post-Operative Cognitive Dysfunction.Lancet,1998 Mar 21,351(9106):857-61.
[7]Monk TG,Weldon BC,Garvan CW,et al.Predictors of cognitive dysfunction after major noncardiac surgery.Anesthesiology,2008 Jan,108(1):18-30.
[8]初学亮.丙泊酚和异氟烷对老年病人全麻术后认知功能影响的比较.中华医学实践杂志,2006,5(10):1089-1092.
[9]吴涯雯,曾静贤.老年人术后认知功能障碍的探讨.青海医药杂志,2005,35(11):12-3.
[10]谭刚,郭向阳,罗爱伦.评价手术后病人神经心理改变时值得注意的几个问题.中华麻醉学杂志,2004,24(6):477-79.
[11]Basile AM,Fusi C,Conti AA,et al.S-100 protein and neuron-specific enolase as markers of subclinical cerebral damage after cardiac surgery:preliminary observation of a 6-month follow-up study.Eur Neurol,2001,45(3):151-9.
[12]Rasmussen LS,Christiansen M,Hansen PB,et al.Do blood levels of neuron-specific enolase and S-100 protein reflect cognitive dysfunction after coronary artery bypass? Acta Anaesthesiol Scand,1999 May,43(5):495-500.
[13]郭向阳,罗爱伦,尹毅青,等.冠状动脉搭桥术患者围术期血浆神经元特异性烯醇化酶浓度与术后认知功能.基础医学与临床,2005,25(10):934-7
[14]洪涛,闻大翔,杭燕南.血清S100ββ变化与老年患者腹部手术后认知功能障碍的关系.临床麻醉学杂志,2006,22(8):571-3
[15]李国才,招伟贤.载脂蛋白E基因多态性与认知损害.国外医学.麻醉学与复苏分册,2005,26(4)212-214
[16]Corzo L,Zas R,Rodriguez S,et al.Decreased levels of serum nitric oxide in different forms of dementia.Neurosci Lett,2007 Jun 15,420(3):263-7.
[17]Iohom G,Szarvas S,Larney V,et al.Perioperative plasma concentrations of stable nitric oxide products are predictive of cognitive dysfunction after laparoscopic cholecystectomy.Anesth Analg,2004 Oct,99(4):1245-52,table of contents.
[18]Harmon D,Eustace N,Ghori K,et al.Plasma concentrations of nitric oxide products and cognitive dysfunction following coronary artery bypass surgery.Eur J Anaesthesiol,2005 Apr,22(4):269-76.
[19]Müller SV,Krause N,Schmidt M,et al.Cognitive dysfunction after abdominal surgery in elderly patients.Z Gerontol Geriatr,2004 Dec,37(6):475-85.
[20]Biedler A,Juckenh(o|¨)fel S,Larsen R,et al.Postoperative cognition disorders in elderly patients.The results of the "International Study of Postoperative Cognitive Dysfunction" ISPOCD 1).Anaesthesist,1999 Dec,48(12):884-95.
[21]Cohendy R,Brougere A,Cuvillon P.Anaesthesia in the older patient.Curr Opin Clin Nutr Metab Care,2005 Jan,8(1):17-21.
[22]Bickel H,Gradinger R,Kochs E,et al.Incidence and risk factors of delirium after hip surgery.Psychiatr Prax,2004 Oct,31(7):360-5.
[23]陈雯洁,俞茂华.老年人认知功能损害的危险因素.中华老年多器官疾病杂志,2005,4(2):146-148.
[24]张微微.心脑血管疾病危险因素与认知功能障碍.中华内科杂志,2005,44(10):797-798
[25]Hanon O,Seux ML,Lenoir H,et al.Cognitive functions and hypertension.Arch Mal Coeur Vaiss,2005 Feb,98(2):133-9.
[26]孙纭,张晨.血压与认知功能障碍.国外医学脑血管疾病分册,2004,12(10):750-752.
[27]Rasmussen LS,Johnson T,Kuipers HM,et al.Does anaesthesia cause postoperative cognitive dysfunction? A randomised study of regional versus general anaesthesia in 438 elderly patients.Acta Anaesthesiol Scand,2003 Mar,47(3):260-6.
[28]Papaioannou A,Fraidakis O,Michaloudis D,et al.The impact of the type of anaesthesia on cognitive status and delirium during the first postoperative days in elderly patients.Eur J Anaesthesiol,2005 Jul,22(7):492-9.
[29]Wu CL,Hsu W,Richman JM,Raja SN.Postoperative cognitive function as an outcome of regional anesthesia and analgesia.Reg Anesth Pain Med,2004May-Jun,29(3):257-68.
[30]Farag E,Chelune GJ,Schubert A,et al.Is depth of anesthesia,as assessed by the Bispectral Index,related to postoperative cognitive dysfunction and recovery?Anesth Analg,2006 Sep,103(3):633-40.
[31]蔡一榕,薛张纲,朱彪.患者术后认知功能障碍的危险因素分析.临床麻醉学杂志,2006,22(8):608-610.
[32]曾涛,温剑虎.术后认知功能障碍.中国行为医学科学,2005,14(11):1055-6.
[33]尚游,姚尚龙．全身麻醉药物与学习记忆．临床麻醉学杂志,2006,22(10)：805-806．
[34]Culley DJ,Baxter MG,Crosby CA,et al.Impaired acquisition of spatial memory2 weeks after isoflurane and isoflurane2nit rous oxide anest hesia in aged rat s.Anest h Analg,2004,99:1393-1397.
[35]Rammes G,Starker LK,Haseneder R,et al.Isoflurane anaesthesia reversibly improves cognitive function and long-term potentiation(LTP)via an up-regulation in NMDA receptor 2B subunit expression.Neuropharmacology,2009 Mar,56(3):626-36.
[36]Kanbak M,Saricaoglu F,Akinci SB,et al.The effects of isoflurane,sevoflurane,and desflurane anesthesia on neurocognitive outcome after cardiac surgery:a pilot study.Heart Surg Forum,2007,10(1):E36-41.
[37]Kadoi Y,Goto F.Sevoflurane anesthesia did not affect postoperative cognitive dysfunction in patients undergoing coronary artery bypass graft surgery.J Anesth,2007,21(3):330-5.
[38]Lofwall MR,Griffiths RR,et al.Cognitive and subjective acute dose effects of intramuscular ketamine in healthy adults.Exp Clin Psychopharmacol,2006 Nov,14(4):439-49.
[39]Morgan CJ,Mofeez A,Brandner B,et al.Acute effects of ketamine on memory systems and psychotic symptoms in healthy volunteers.Neuropsychopharmacology,2004Jan,29(1):208-18.
[40]Coull JT,Middleton HC,Robbins TW,et al.Contrasting effects of clonidine and diazepam on tests of working memory and planning.Psychopharmacology(Berl),1995 Aug,120(3):311-21.
[41]Qian YN,Zhang Z,Meng X.Changes of cognitive function after open heart surgery with cardiopulmonary bypass:study of 50 cases.Zhonghua Yi Xue Za Zhi,2005 Jun 1,85(20):1400-2
[42]张富军,罗艳,于布为.术中调控PaCO_2对OPCAB患者术后认知功能的影响.上海交通大学学报(医学版),2006,26(3):288-290.
[43]Newman MF,Kramer D,Croughwell ND,et al.Differential age effect s of mean arterial pressure and rewarming on cognitive dysfunction after cardiac surgery.Anesth Analg,1995,81(2):236-42.
[44]张挺杰,皋源,江燕,等.老年患者术后精神障碍的发生率和病因分析.临床麻醉学杂志,2003,19(2):98-99.
[45]Biedler A,Juckenh(o|¨)fel S,Larsen R,et al.Postoperative cognition disorders in elderly patients.The results of the "International Study of Postoperative Cognitive Dysfunction" ISPOCD 1).Anaesthesist,1999 Dec,48(12):884-895.
[46]Muller SV,Krause N,Schmidt M,et al.Cognitive dysfunction after abdominal surgery in elderly patients.Z Gerontol Geriatr,2004,37:475-485.
[47]钱怡宁,张茁,孟旭.心内直视手术患者围术期认知功能的变化.中华医学杂志,2005,85(20):1400-1402.
[48]刘胜中,杨双强.体外循环心脏术后精神障碍.中国体外循环杂志,2007,5(1):54-56.
[49]Grigore AM,Grocott HP,Mathew JP,et al.The rewarming rate and increased peak temperature alter neurocognitive outcome after cardiac surgery.Anesth Analg,2002,94(l):4-10.
[50]Edmonds CR,Barbut D,Hager D,et al.Intraoperative cerebral arterial embolization during total hip arthroplasty.Anesthesiology,2000,93(2):315-318.
[51]Bickel H,Gradinger R,Kochs E,et al.Incidence and risk factors of delirium after hip surgery.Psychiatr Prax,2004 Oct,31(7):360-365.
[52]SoRelle R.Fever after coronary artery bypass graft surgery increases likelihood of cognitive loss.Circulation,2002 Feb 12,105(6):e9073-4.
[53]Grocott HP.Hyperglycemia and postoperative cognitive dysfunction:another call for better glycemic control? Can J Anaesth,2008 Mar,55(3):140-5.
[54]Veliz-Reissmiiller G,Agiiero Torres H,et al.Pre-operative mild cognitive dysfunction predicts risk for post-operative delirium after elective cardiac surgery.Aging Clin Exp Res,2007 Jun,19(3):172-7.
[55]Fearn SJ,Pole R,Wesnes K,et al.Cerebral injury during cardio-pulmonary bypass:emboli impair memory.J Thorac Cardiovasc Surg,2001,121(6):1150-1160.
[56]Robert P.Understanding and managing behavioural symptoms in Alzheimer's disease and related dementias:focus on rivastigmine.Curr Med Res Opin,2002,18(3):156-71.
[57]Narahashi T,Marszalec W,Moriguchi S,et al.Unique mechanism of action of Alzheimer's drugs on brain nicotinic acetylcholine receptors and NMDA receptors.Life Sci,2003 Dec 5,74(2-3):281-91.
[58]李茂全,王艳艳,余争平.糖皮质激素对海马功能损伤机制的研究进展.重庆医学,2006,35(12):1124-26.
[59]Wang D,Wu X,Li J,et al.The effect of lidocaine on early postoperative cognitive dysfunction after coronary artery bypass surgery.Anesth Analg,2002Nov,95(5):1134-41,table of contents.
[60]王东信,吴新民,李军,等.利多卡因对心脏手术后病人早期认知功能障碍发生率的影响.中华麻醉学杂志,2004,24(2):85-88.
[2]Bugianesi E,McCullough AJ,Marchesini G:Insulin resistance:a metabolic pathway to chronic liver disease.Hepatology,2005;42:987-1000,
[3]Buyse S,Valla D.Carbohydrate metabolism dysregulation in cirrhosis:pathophysiology,prognostic impact and therapeutic implications.Gastroenterol Clin Biol,2007 Mar;31(3):266-73.
[4]Perseghin G,Mazzaferro V,Sereni LP,et al.Contribution of reduced insulin sensitivity and secretion to the pathogenesis of hepatogenous diabetes:effect of liver transplantation.Hepatology,2000 Mar;31(3):694-703.
[5]Mastsumoto D,Yamanaka-Okumura H,et al.Nutritional treatment of a patient with hepatic cirrhosis with the novel low glycemic index liquid food(Inslow).J Med Invest,2007 Aug;54(3-4):375-80.
[6]Lincano JM,Alessi DR.The Insulin Signalling Pathway.Curr.Biol,2002;12(7):R236-238
[7]Asano T,Fujishiro M,Kushiyama A,et al.Role of phosphatidylinositol 3-kinase activation on insulin action and its alteration in diabetic conditions.Biol Pharm Bull,2007 Sep;30(9):1610-6.
[8]Furtado LM,Somwar R,Sweeney G,et al.Activation of the glucose transporter GLUT4 by insulin.Biochem Cell Biol,2002;80(5):569-78.
[9]Wallberg-Henriksson H,Zierath JR.GLUT4:a key player regulating glucose homeostasis? Insights from transgenic and knockout mice(review).Mol Membr Biol,2001 Jul-Sep;18(3):205-11.
[10]Chang L,Chiang SH,Saltiel AR.Insulin signaling and the regulation of glucose transport.Mol Med,2004 Jul-Dec;10(7-12):65-71
[11]Asano T,Fujishiro M,Kushiyama A,ET AL.Role of phosphatidylinositol 3-kinase activation on insulin action and its alteration in diabetic conditions.Biol Pharm Bull,2007 Sep;30(9):1610-6.
[12]Mott DM,Kida Y,Nyomba BL.Human skeletal muscle type-1 protein phosphatase and insulin resistance.Adv.prot.phosph,1993,7(11):413-417
[13]Ericsson A,Hamark B,Powell TL,et al.Glucose transporter isoform 4 is expressed in the syncytiotrophoblast of first trimester human placenta.Hum Reprod,2005,20:521-30.
[14]Garvey WT,Maianu L,Hancock JA,et,al.Gene expression of GLUT4 in skeletal muscle from insulin resistant patients with obesity,IGT,GDM,and NIDDM.Diabetes,1992;41:465-475.
[15]Pedersen O,Bak JF,Andersen PH,et al.Evidence against altered expression of GLUT1 or GLUT4 in skeletal muscle of patients with obesity or NIDDM.Diabetes,1990;39:865-870.
[16]Mirela D,Christopher GA,Lorraine D.Disruption of the Striated Muscle Glycogen Targeting Subunit PPP1R3A of Protein Phosphatase 1 Leads to Increased Weight Gain,Fat Deposition,and Development of Insulin Resistance.Diabetes,2003,52(3):596-604
[17]David B Savage,Lanmin Zhai,Balasubramanian Ravikumar,et al.A Prevalent Variant in PPP1R3A Impairs Glycogen Synthesis and Reduces Muscle Glycogen Content in Humans and Mice.Mol Cell Endocrinol,2008 Mar 26;285(1-2):10-8.
[18]James X,Clifton B,Michal P.A Type 2 Diabetes-Associated Polymorphic ARE Motif Affecting Expression of PPP1R3 Is Involved in RNA-Protein Interactions.Molecular Genetics and Metabolism,1999,68(6):48-55
[19]Riggio O,Merli M,Leonetti F,et al.Impaired nonoxidative glucose metabolism in patients with liver cirrhosis:effects of two insulin doses.Metabolism,1997 Jul;46(7):840-3.
[20]Kruszynska Y,Williams N,Perry M,Home P.The relationship between insulin sensitivity and skeletal muscle enzyme activities in hepatic cirrhosis.Hepatology,1988 Nov-Dec;8(6):1615-9.
[21]Schneiter P,Gillet M,Chioléro R,et al.Hepatic nonoxidative disposal of an oral glucose meal in patients with liver cirrhosis.Metabolism.1999 Oct;48(10):1260-6
[22]Shmueli E,Walker M,Alberti G,Record CO.Hepatology.Normal splanchnic but impaired peripheral insulin-stimulated glucose uptake in cirrhosis,1993 Jul;18(1):86-95.
[23]Karnieli E,Armoni M.Transcriptional regulation of the insulin- responsive glucose transporter GLUT4 gene:from physiology to pathology.Am J Physiol Endocrinol Metab,2008 Jul;295(1):E38-45.
[24]张霞,沈鼎明.肝源性糖尿病的研究进展.中华肝脏病杂志,2002;10(6):476-8
[25]Kuriyama S,Miwa Y,Fukushima H,et al.Prevalence of diabetes and incidence of angiopathy in patients with chronic viral liver disease.J Clin Biochem Nutr,2007 Mar;40(2):116-22.
[26]Postic C,Girard J.Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance:lessons from genetically engineered mice.J Clin Invest,2008 Mar;118(3):829-38.
[27]施红梅,孟祥伟.肝源性糖尿病发病机制的研究进展.吉林医学,2007;28(2):178-9.
[28]Nikoulina SE,Ciaraldi TP,Abrams-Carter L,et al.Regulation of glycogen synthase activity in cultured skeletal muscle cells from subjects with type Ⅱdiabetes:role of chronic hyperinsulinemia and hyperglycemia.Diabetes,1997 Jun;46(6):1017-24.
[29]Zhang Y,Guan L,Wang X,et al.Protection of chlorophyllin against oxidative damage by inducing HO-1 and NQO1 expression mediated by PI3K/Akt and Nrf2.Free Radic Res,2008 Apr;42(4):362-71.
[30]Elisabeth S,Daniel B,Joan C,et al.A Novel Role of Neuregulin in Skelet al Muscle.The Journal of Biological Chemistry,2001,276(21):18257-18264.
[31]Watson R T,Pessin J.Intracelular organization of insulin signaling and GLUT4 translocation.Recent Prog Horm Res,2001(7),56:175-193.
[32]Holland-Fischer P,Anderson PH,Lund S,et al.Muscle GLUT4 in cirrhosis.J Hepatol,2007,47:212-219.
[33]Maureen J,Charron S,Ellen B,et al.GLUT4 gene regulation and manipulation.Biol Chem,1999,274:3253-3256.
[34]Jessen N,Buhl ES,Schmitz O,et,al.Impaired insulin action despite upregulation of proximal insulin signaling:novel insights into skelet al muscle insulin resistance in liver cirrhosis.J Hepatol,2006 Dec;45(6):797-804.
[35]Kelley DE,Mintun MA,Watkins SC,et al.The effect of non-insulin-dependent diabetes mellitus and obesity on glucose transport and phosphorylation in skelet al muscle.J Clin Invest,1996 Jun 15;97(12):2705-13.
[36]Ryder J W,Yang J,Galuska D,et al.Use of a novel impermeable biotinylated photolabeling reagent to assess insulin-and hypoxia-stimulated cell surface GLUT4 content in skelet al muscle from type 2 diabetic patients.Diabetes,2000,49:647-654.
[37]Nielsen MF,Caumo A,Aagaard NC,et al.Contribution of defects in glucose uptake to carbohydrate intolerance in liver cirrhosis:assessment during physiologic glucose and insulin concentrations.Am J Physiol Gastrointest Liver Physiol,2005,32:34-39
[38]Doney AS,Fischer B,Cecil JE,et al.Male preponderance in early diagnosed type 2 diabetes is associated with the ARE insertion/deletion polymorphism in the PPPlR3Alocus.BMC Genet,2003,4:11.
[39]Mammarella S,Creati B,Staniscia T,et al.Obesity modifies the effects of the Asp905Tyr variant of PPP1R3A on risk of type 2 diabetes and insulin sensitivity.Diabetes Obes Metab,2007 Sep,9(5):759-61.
[40]Bak JF.Insulin receptor function and glycogen synthase activity in human skelet al muscle.Physiology and pathophysiology.Dan Med Bull,1994 Apr,41(2):179-92.
[41]Kakizaki S,Sohara N,Yamazaki Y,et al.Elevated plasma resistin concentrations in patients with liver cirrhosis.J Gastroenterol Hepatol,2008 Jan,23(1):73-77
[42]Kraegen EW,Cooney GJ.Free fatty acids and skelet al muscle insulin resistance.Curr Opin Lipidol,2008 Jun,19(3):235-41.
[43]Griffin ME,Mareueei MJ,Cline GW,et al.Free fatty acid induced insulin resistance is associated with activation of protein kinase C theta and alterations in the insulin signaling cascade.Diabetes,1999,48(6):1270-1274.
[44]Ruddock MW,Stein A,Landaker E,et al.Saturated fatty acids inhibit hepatic insulin action by modulating insulin receptor expression and post-receptor signalling.J Biochem,2008 Nov,144(5):599-607.
[45]Seirafi M,Negro F.Hepatitis C and insulin resistance.Rev Med Suisse,2008,4(169):1859-62.
[46]Aytug S,Reich D,Sapiro LE,et al.Impaired IRS-1/PI3-kinase signaling in patients with HCV:a mechanism for increased prevalence of type 2 diabetes.Hepatology,2003 Dec,38(6):1384-92.
[47]Ryder JW,Gilbert M,Zierath JR.Skelet al muscle and insulin sensitivity:pathophysiological alterations.Front Biosci,2001,6:D154-63.
[1]Grocott HR Hyperglycemia and postoperative cognitive dysfunction:another call for better glycemic control?Can J Anaesth,2008 Mar,55(3):140-5.
[2]Jones R Perioperative glycemic control and postoperative cognitive dysfunction:an expression of caution.Can J Anaesth,2008 Aug,55(8):559-60;
[3]Ammori JB,Sigakis M,Englesbe MJ,et al.Effect of intraoperative hyperglycemia during liver transplantation.J Surg Res,2007 Jun,140(2):227-33.
[4]Saliba F,Lakehal M,Pageaux GP,et al.Risk factors for new-onset diabetes mellitus following liver transplantation and impact of hepatitis C infection:an observational multicenter study.Liver Transpl,2007,13(1):5-7.
[5]Bianchi G,Marchesini G,Marzocchi R,Metabolic syndrome in liver transplantation:relation to etiology and immunosuppression.Liver Transpl,2008 Nov,14(11):1648-54
[6]Cooper ME,Tikellis C,Thomas MC:Preventing diabetes in patients with hypertension:One more reason to block the renin-angiotensin system.J Hypertens Suppl,2006,24:S57-S63
[7]Shinozaki K,Ayajiki K,Nishio Y,et al.Evidence for a causal role of the renin-angiotensin system in vascular dysfunction associated with insulin resistance.Hypertension,2004,43:255-262
[8]Bloom RD,Crutchlow MF.Transplant-associated hyperglycemia.Transplant Rev(Orlando).2008 Jan,22(1):39-51.
[9]Marie Laryea,Kymberly D.Watt,Michele Molinari,et,al.Metabolic Syndrome in Liver Transplant Recipients:Prevalence and Association With Major Vascular Events.LIVER TRANSPLANTATION,2007,13:1109-1114
[10]DeWolf AM,Kang YG,Todo S,Kam I,et al.Glucose metabolism during liver transplantation in dogs.Anesth Analg,1987,66(1):76-80.
[11]Ichimiya M,Takada Y,Shimahara Y,et al.Insulin and glucagon levels in living related liver transplantation:their interaction with the recovery of graft liver function.Transpl Int,1995,8(3):165-168.
[12]Perseghin G,Regalia E,Battezzati A,et al.Regulation of glucose homeosta tasis in humans with denervated livers.J Clin Invest,1997,100(4):931-941.
[13]Shangraw RE,Hexem JG.Glucose and potassium metabolic responses to insulin during liver transplantation.Liver Transpl Surg,1996,2(6):443-454.
[14]Thorell A,Nygren J,Ljungqvist O.Insulin resistance:a marker of surgical stress.Curr Opin Clin Nutr Metab Care,1999 Jan,2(1):69-78.
[15]Soop M,Nygren J,Thorell A,et al.Stress-induced insulin resistance:recent developments.Curr Opin Clin Nutr Metab Care,2007 Mar,10(2):181-6.
[16]Asano T,Fujishiro M,Kushiyama A,et al.Role of phosphatidylinositol 3-kinase activation on insulin action and its alteration in diabetic conditions.Biol Pharm Bull,2007 Sep,30(9):1610-6.
[17]Furtado LM,Somwar R,Sweeney G,et al.Activation of the glucose transporter GLUT4 by insulin.Biochem Cell Biol,2002,80(5):569-78.
[18]Thirone AC,Carvalheira JB,Hirata AE,et al.Regulation of Cbl-associated protein/Cb1 pathway in muscle and adipose tissues of two animal models of insulin resistance.Endocrinology,2004 Jan,145(1):281-93.
[19]Chang L,Chiang SH,Saltiel AR.Insulin signaling and the regulation of glucose transport.Mol Med,2004 Jul-Dec,10(7-12):65-71
[20]Pedersen O,Bak JF,Andersen PH,et al.Evidence against altered expression of GLUT1 or GLUT4 in skelet al muscle of patients with obesity or NIDDM.Diabetes,1990,39:865-870.
[21]Ericsson A,Hamark B,Powell TL,et al.Glucose transporter isoform 4 is expressed in the syncytiotrophoblast of first trimester human placenta.Hum Reprod,2005,20:521-30.
[22]Garvey WT,Maianu L,Hancock JA,et,al.Gene expression of GLUT4 in skeletal muscle from insulin resistant patients with obesity,IGT,GDM,and NIDDM.Diabetes,1992,41:465-475.
[23]Mott DM,Kida Y,Nyomba BL.Human skeletal muscle type-1 protein phosphatase and insulin resistance.Adv.prot.phosph,1993,7(11):413-417.
[24]Mirela D,Christopher GA,Lorraine D.Disruption of the Striated Muscle Glycogen Targeting Subunit PPP1R3A of Protein Phosphatase 1 Leads to Increased Weight Gain,Fat Deposition,and Development of Insulin Resistance.Diabetes,2003,52(3):596-604.
[25]David B Savage,Lanmin Zhai,Balasubramanian Ravikumar,et al.A Prevalent Variant in PPP1R3A Impairs Glycogen Synthesis and Reduces Muscle Glycogen Content in Humans and Mice.Mol Cell Endocrinol,2008 Mar 26,285(1-2):10-8.
[26]Malecki MT.Genetics of type 2 diabetes mellitus.Diabetes Res Clin Pract,2005Jun,68 Suppll:S10-21.
[27]Buyse S,Valla D.Carbohydrate metabolism dysregulation in cirrhosis:pathophysiology,prognostic impact and therapeutic implications.Gastroenterol Clin Biol,2007 Mar,31(3):266-73.
[28]Perseghin G,Mazzaferro V,Sereni LP,et al.Contribution of reduced insulin sensitivity and secretion to the pathogenesis of hepatogenous diabetes:effect of liver transplantation.Hepatology,2000 Mar,31(3):694-703.
[29]施红梅,孟祥伟.肝源性糖尿病发病机制的研究进展.吉林医学,2007,28(2):178-179.
[30]Perseghin G,Mazzaferro V,Sereni LP,et al.COntrmutiOn of reduced insulin sensitivity and secretion to the pathogenesis of hepatogenous diabetes:effect of liver transplantation.Hepatology,2000,31:694-703.
[31]Schneiter P,Gillet M,Chioléro R,et al.Mechanisms of postprandial hyperglycemia in liver transplant recipients:comparison of liver transplant patients with kidney transplant patients and healthy controls.Diabetes Metab,2000 Feb,26(1):51-6.
[32]Riggio O,Merli M,Leonetti F,et al.Impaired nonoxidative glucose metabolism in patients with liver cirrhosis:effects of two insulin doses.Metabolism,1997Jul,46(7):840-3.
[33]Shmueli E,Walker M,Alberti G,Record CO.Hepatology.Normal splanchnic but impaired peripheral insulin-stimulated glucose uptake in cirrhosis,1993 Jul,18(1):86-95.
[34]Kruszynska Y,Williams N,Perry M,Home P.The relationship between insulin sensitivity and skeletal muscle enzyme activities in hepatic cirrhosis.Hepatology,1988 Nov-Dec,8(6):1615-9.
[35]Schneiter P,Gillet M,Chioléro R,et al.Hepatic nonoxidative disposal of an oral glucose meal in patients with liver cirrhosis.Metabolism,1999 Oct,48(10):1260-6
[36]Tietge UJ,Selberg O,Kreter A,et al.Alterations in glucose metabolism associated with liver cirrhosis persist in the clinically stable long-term course after liver transplantation.Liver Transpl,2004 Aug,10(8):1030-40.
[37]Xue C,Aspelund G,Sritharan KC,et al.Isolated hepatic cholinergic denervation impairs glucose and glycogen metabolism.J Surg Res,2000 May 1,90(l):19-25.
[38]Latour MG,Lautt WW.Auton Neurosci.The hepatic vagus nerve in the control of insulin sensitivity in the rat,2002 Jan 10,95(1-2):125-30.
[39]Matsuhisa M,Yamasaki Y,Shiba Y,et al.Important role of the hepatic vagus nerve in glucose uptake and production by the liver.Metabolism,2000 Jan,49(1):11-6.
[40]Dicostanzo CA,Dardevet DP,Neal DW,et al.Role of the hepatic sympathetic nerves in the regulation of net hepatic glucose uptake and the mediation of the portal glucose signal.Am J Physiol Endocrinol Metab,2006 Jan,290(l):E9-E16.
[41]王丽静,刘礼斌.糖皮质激素诱导胰岛素抵抗的分子机制.国际内分泌代谢 杂志,2007,27(6):415-417
[42]Liu C,Wang X,Chen Z,Zhang L,Wu Y,Zhang Y.Hepatic ischemia-reperfusion induces insulin resistance via down-regulation during the early steps in insulin signaling in rats.Transplant Proc,2008 Dec,40(10):3330-4.
[43]Ogawa W,Kasuga M.Insulin signaling and pathophysiology of type 2 diabetes mellitus.Nippon Rinsho,2006 Jul,64(7):1381-9.
[1]Mora PF.Post-transplantation diabetes mellitus.Am J Med Sci,2005 Feb,329(2):86-94.
[2]Saliba F,Lakehal M,Pageaux GP,et al.Risk factors for new-onset diabetes mellitus following liver transplantation and impact of hepatitis C infection:an observational multicenter study.Liver Transpl,2007,13(l):5-7.
[3]Bianchi G,Marchesini G,Marzocchi R,et al.Metabolic syndrome in liver transplantation:relation to etiology and immunosuppression.Liver Transpl,2008Nov,14(11):1648-54.
[4]Bloom RD,Crutchlow MF.Transplant-associated hyperglycemia.Transplant Rev (Orlando),2008 Jan,22(1):39-51.
[5]Grocott HP.Hyperglycemia and postoperative cognitive dysfunction:another call for better glycemic control? Can J Anaesth,2008 Mar,55(3):140-5.
[6]Jones P.Perioperative glycemic control and postoperative cognitive dysfunction:an expression of caution.Can J Anaesth,2008 Aug,55(8):559-60.
[7]Cooper ME,Tikellis C,Thomas MC:Preventing diabetes in patients with hypertension:One more reason to block the renin-angiotensin system.J Hypertens Suppl,2006,24:S57-S63.
[8]Shinozaki K,Ayajiki K,Nishio Y,et al.Evidence for a causal role of the renin-angiotensin system in vascular dysfunction associated with insulin resistance.Hypertension,2004,43:255-262.
[9]Marie Laryea,Kymberly D.Watt,Michele Molinari,et,al.Metabolic Syndrome in Liver Transplant Recipients:Prevalence and Association With Major Vascular Events.LIVER TRANSPLANTATION,2007,13:1109-1114.
[10]余自成,张可蹭.移植后新发生糖尿病治疗和管理指南.世界临床药物,2006,26(9):518-522.
[11]Rabkin JM,Corless CL,Rosen HR,et al.Imnmnosuppression impact on lang-term cardiovascular complications after liver transplantation.Am J Surg,2002,183(5):595-599.
[12]陈琳,盛正妍,王煜非.移植后糖尿病的危险因素及其发病机制的研究进展.中华全科医师杂志,2007,6(3):160-162.
[13]张霞,沈鼎明.肝源性糖尿病的研究进展.中华肝脏病杂志,2002,10(6):476-478.
[14]施红梅,孟祥伟.肝源性糖尿病发病机制的研究进展.吉林医学,2007,28(2):178-180.
[15]Depczynski B,Daly B,Campbell LV,et al.Predicting the occurrence of diabetes mellitus in recipients of heart transplants.Diabet Med,2000 Jan,17(1):15-9.
[16]Hakan K.R.Karlsson,Maria Ahlse'n,Juleen R.Zierath,et al.Insulin Signaling and Glucose Transport in Skeletal Muscle From First-Degree Relatives of Type 2Diabetic Patients.DIABETES,VOL.55,MAY 2006:1283-1288.
[17]Hoban R,Gielda B,Temkit M,et al.Utility of HbA1c in the detection of subclinical post renal transplant diabetes.Transplantation,2006 Feb 15,81(3):379-83.
[18]Torres-Romero LF,Santiago-Delpin EA,de Echegaray S,et al.HLA is not predictive of posttransplant diabetes mellitus.Transplant Proc,2006 Apr,38(3):914-5.
[19]Steinmüller TH,Stockmann M,Bechstein WO,et al.Liver transplantation and diabetes mellitus.Exp Clin Endocrinol Diabetes.2000;108(6):401-5.
[20]Delgado-Borrego A,Casson D,Sehoenfeld D,et al.Hepatitis C virus is independently associated with increased insulin resistance after liver transplantation.Transplantation,2005,77(5):703-710.
[21]Masini M,Campani D,Boggi U,et al.Hepatitis C virus infection and human pancreatic beta-cell dysfunction.Diabetes Care,2005,28(4):940-941.
[22]Neylan JF.Racial differences in renal transplantation after immunosuppression with tacrolimus versus cyclosporine.FK506 Kidney Transplant Study Group.Transplantation,1998 Feb 27,65(4):515-23.
[23]Walczak D,Calvert D,Oberholzer J,et al.Effect of race on the occurrence of posttransplant diabetes in kidney transplant recipients treated with early steroid discontinuation.Transplant Proc,2005 Mar,37(2):819-21
[24]Baltar J,Ortega T,Ortega F,et al.Posttransplantation diabetes mellitus:prevalence and risk factors.Transplant Proc,2005 Nov,37(9):3817-8.
[25]冉兴无.FK506与器官移植术后糖尿病.国外医学泌尿系统分册,2005,25(4):566-568
[26]Campise M.Post-transplant diabetes mellitus:diagnosis and treatment.G Ital Nefrol,2007 Nov-Dec,24 6):547-57.
[27]王丽静,刘礼斌.糖皮质激素诱导胰岛素抵抗的分子机制.国际内分泌代谢杂志,2007,27(6):415-417.
[28]李新,袁莉.移植后糖尿病研究进展,国际移植.血液净化杂志,2006,4(1):38-40.
[29]Midtvedt K,Hjelmesaeth J,Hartmann A,et al.Insulin resistance after renal transplantation:the effect of steroid dose reduction and withdrawal.J Am Soc Nephrol,2004 Dec,15(12):3233-9.
[30]Burroughs TE,Lentine KL,Takemoto SK,et al.Influence of early posttransplantation prednisone and calcineurin inhibitor dosages on the incidence of new-onset diabetes.Clin J Am Soc Nephrol,2007,2(3):517-23.
[31]Rabkin JM,Corless CL,Rosen HR,et al.Immunosuppression impact on long-term cardiovascular complications after liver transplantation.Am J Surg,2002,183(5):595-9.
[32]32:Redmon JB,Olson LK,Armstrong MB,et al.Effects of tacrolimus(FK506)on human insulin gene expression,insulin mRNA levels,and insulin secretion in HIT-T15 cells.J Clin Invest,1996,15,98(12):2786-93.
[33]鞠卫强,何晓顺.肝移植术后代谢并发症.中华肝胆外科杂志,2003,9(5):315-317.
[34]Stockmann M,Konrad T,Nolting S,et al.Major influence of liver function itself but not of immunosuppression determines glucose tolerance after living-donor liver transplantation.Liver Transpl,2006 Apr,12(4):535-543.
[35]Tappy L,Schneiter P,Chiolero R,et al.Effects of a glucose meal on energy metabolism in patients with cirrhosis before and after liver transplantation.Arch Surg,2001 Jan,136(1):80-4.
[36]Colle Ⅰ,Van Vlierberghe H,Troisi R,et al.Transplanted liver:consequences of denervation for liver functions.Anat Rec A Discov Mol Cell Evol Biol,2004 Sep,280(1):924-31.
[37]Kissler HJ,Hauffen J,Hennig R,et al.Glucose and lipid metabolism after liver transplantation in inbred rats:consequences of hepatic denervation.Metabolism,2005 Jul,54(7):881-90.
[38]Schneiter P,Gillet M,Chiolero R,et al.Mechanisms of postprandial hyperglycemia in liver transplant recipients:comparison of liver transplant patients with kidney transplant patients and healthy controls.Diabetes Metab,2000 Feb,26(1):51-6.
[39]39.Schneiter P,Gillet M,Chiolero R,et al.Postprandial hepatic glycogen synthesis in liver transplant recipients.Transplantation,2000 Mar 15,69(5):978-81
[1]Sophie S.Anaesthesia for the elderly patient.J Pak Med Assoc,2007 Apr,57(4):196-201.
[2]Bekker AY,Weeks EJ.Cognitive function after anaesthesia in the elderly.Best Pract Res Clin Anaesthesiol,2003 Jun,17(2):259-72.
[3]Dodds C,Allison J.Postoperative cognitive deficit in the elderly surgical patient.Br J Anaesth,1998 Sep,81(3):449-62.
[4]姚立农,张宏.老年人术后认知功能障碍的研究现状.国外医学麻醉与复苏分册,200 1,22(4):217-220.
[5]Laalou FZ,Carre AC,Forestier C,et al.Pathophysiology of post-operative cognitive dysfunction:current hypotheses.J Chir(Paris),2008 Jul-Aug,145(4):323-30.
[6]Moller JT,Cluitmans P,Rasmussen LS,et al.Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study.ISPOCD investigators.International Study of Post-Operative Cognitive Dysfunction.Lancet,1998 Mar 21,351(9106):857-61.
[7]Monk TG,Weldon BC,Garvan CW,et al.Predictors of cognitive dysfunction after major noncardiac surgery.Anesthesiology,2008 Jan,108(1):18-30.
[8]初学亮.丙泊酚和异氟烷对老年病人全麻术后认知功能影响的比较.中华医学实践杂志,2006,5(10):1089-1092.
[9]吴涯雯,曾静贤.老年人术后认知功能障碍的探讨.青海医药杂志,2005,35(11):12-3.
[10]谭刚,郭向阳,罗爱伦.评价手术后病人神经心理改变时值得注意的几个问题.中华麻醉学杂志,2004,24(6):477-79.
[11]Basile AM,Fusi C,Conti AA,et al.S-100 protein and neuron-specific enolase as markers of subclinical cerebral damage after cardiac surgery:preliminary observation of a 6-month follow-up study.Eur Neurol,2001,45(3):151-9.
[12]Rasmussen LS,Christiansen M,Hansen PB,et al.Do blood levels of neuron-specific enolase and S-100 protein reflect cognitive dysfunction after coronary artery bypass? Acta Anaesthesiol Scand,1999 May,43(5):495-500.
[13]郭向阳,罗爱伦,尹毅青,等.冠状动脉搭桥术患者围术期血浆神经元特异性烯醇化酶浓度与术后认知功能.基础医学与临床,2005,25(10):934-7
[14]洪涛,闻大翔,杭燕南.血清S100ββ变化与老年患者腹部手术后认知功能障碍的关系.临床麻醉学杂志,2006,22(8):571-3
[15]李国才,招伟贤.载脂蛋白E基因多态性与认知损害.国外医学.麻醉学与复苏分册,2005,26(4)212-214
[16]Corzo L,Zas R,Rodriguez S,et al.Decreased levels of serum nitric oxide in different forms of dementia.Neurosci Lett,2007 Jun 15,420(3):263-7.
[17]Iohom G,Szarvas S,Larney V,et al.Perioperative plasma concentrations of stable nitric oxide products are predictive of cognitive dysfunction after laparoscopic cholecystectomy.Anesth Analg,2004 Oct,99(4):1245-52,table of contents.
[18]Harmon D,Eustace N,Ghori K,et al.Plasma concentrations of nitric oxide products and cognitive dysfunction following coronary artery bypass surgery.Eur J Anaesthesiol,2005 Apr,22(4):269-76.
[19]Müller SV,Krause N,Schmidt M,et al.Cognitive dysfunction after abdominal surgery in elderly patients.Z Gerontol Geriatr,2004 Dec,37(6):475-85.
[20]Biedler A,Juckenh(o|¨)fel S,Larsen R,et al.Postoperative cognition disorders in elderly patients.The results of the "International Study of Postoperative Cognitive Dysfunction" ISPOCD 1).Anaesthesist,1999 Dec,48(12):884-95.
[21]Cohendy R,Brougere A,Cuvillon P.Anaesthesia in the older patient.Curr Opin Clin Nutr Metab Care,2005 Jan,8(1):17-21.
[22]Bickel H,Gradinger R,Kochs E,et al.Incidence and risk factors of delirium after hip surgery.Psychiatr Prax,2004 Oct,31(7):360-5.
[23]陈雯洁,俞茂华.老年人认知功能损害的危险因素.中华老年多器官疾病杂志,2005,4(2):146-148.
[24]张微微.心脑血管疾病危险因素与认知功能障碍.中华内科杂志,2005,44(10):797-798
[25]Hanon O,Seux ML,Lenoir H,et al.Cognitive functions and hypertension.Arch Mal Coeur Vaiss,2005 Feb,98(2):133-9.
[26]孙纭,张晨.血压与认知功能障碍.国外医学脑血管疾病分册,2004,12(10):750-752.
[27]Rasmussen LS,Johnson T,Kuipers HM,et al.Does anaesthesia cause postoperative cognitive dysfunction? A randomised study of regional versus general anaesthesia in 438 elderly patients.Acta Anaesthesiol Scand,2003 Mar,47(3):260-6.
[28]Papaioannou A,Fraidakis O,Michaloudis D,et al.The impact of the type of anaesthesia on cognitive status and delirium during the first postoperative days in elderly patients.Eur J Anaesthesiol,2005 Jul,22(7):492-9.
[29]Wu CL,Hsu W,Richman JM,Raja SN.Postoperative cognitive function as an outcome of regional anesthesia and analgesia.Reg Anesth Pain Med,2004May-Jun,29(3):257-68.
[30]Farag E,Chelune GJ,Schubert A,et al.Is depth of anesthesia,as assessed by the Bispectral Index,related to postoperative cognitive dysfunction and recovery?Anesth Analg,2006 Sep,103(3):633-40.
[31]蔡一榕,薛张纲,朱彪.患者术后认知功能障碍的危险因素分析.临床麻醉学杂志,2006,22(8):608-610.
[32]曾涛,温剑虎.术后认知功能障碍.中国行为医学科学,2005,14(11):1055-6.
[33]尚游,姚尚龙．全身麻醉药物与学习记忆．临床麻醉学杂志,2006,22(10)：805-806．
[34]Culley DJ,Baxter MG,Crosby CA,et al.Impaired acquisition of spatial memory2 weeks after isoflurane and isoflurane2nit rous oxide anest hesia in aged rat s.Anest h Analg,2004,99:1393-1397.
[35]Rammes G,Starker LK,Haseneder R,et al.Isoflurane anaesthesia reversibly improves cognitive function and long-term potentiation(LTP)via an up-regulation in NMDA receptor 2B subunit expression.Neuropharmacology,2009 Mar,56(3):626-36.
[36]Kanbak M,Saricaoglu F,Akinci SB,et al.The effects of isoflurane,sevoflurane,and desflurane anesthesia on neurocognitive outcome after cardiac surgery:a pilot study.Heart Surg Forum,2007,10(1):E36-41.
[37]Kadoi Y,Goto F.Sevoflurane anesthesia did not affect postoperative cognitive dysfunction in patients undergoing coronary artery bypass graft surgery.J Anesth,2007,21(3):330-5.
[38]Lofwall MR,Griffiths RR,et al.Cognitive and subjective acute dose effects of intramuscular ketamine in healthy adults.Exp Clin Psychopharmacol,2006 Nov,14(4):439-49.
[39]Morgan CJ,Mofeez A,Brandner B,et al.Acute effects of ketamine on memory systems and psychotic symptoms in healthy volunteers.Neuropsychopharmacology,2004Jan,29(1):208-18.
[40]Coull JT,Middleton HC,Robbins TW,et al.Contrasting effects of clonidine and diazepam on tests of working memory and planning.Psychopharmacology(Berl),1995 Aug,120(3):311-21.
[41]Qian YN,Zhang Z,Meng X.Changes of cognitive function after open heart surgery with cardiopulmonary bypass:study of 50 cases.Zhonghua Yi Xue Za Zhi,2005 Jun 1,85(20):1400-2
[42]张富军,罗艳,于布为.术中调控PaCO_2对OPCAB患者术后认知功能的影响.上海交通大学学报(医学版),2006,26(3):288-290.
[43]Newman MF,Kramer D,Croughwell ND,et al.Differential age effect s of mean arterial pressure and rewarming on cognitive dysfunction after cardiac surgery.Anesth Analg,1995,81(2):236-42.
[44]张挺杰,皋源,江燕,等.老年患者术后精神障碍的发生率和病因分析.临床麻醉学杂志,2003,19(2):98-99.
[45]Biedler A,Juckenh(o|¨)fel S,Larsen R,et al.Postoperative cognition disorders in elderly patients.The results of the "International Study of Postoperative Cognitive Dysfunction" ISPOCD 1).Anaesthesist,1999 Dec,48(12):884-895.
[46]Muller SV,Krause N,Schmidt M,et al.Cognitive dysfunction after abdominal surgery in elderly patients.Z Gerontol Geriatr,2004,37:475-485.
[47]钱怡宁,张茁,孟旭.心内直视手术患者围术期认知功能的变化.中华医学杂志,2005,85(20):1400-1402.
[48]刘胜中,杨双强.体外循环心脏术后精神障碍.中国体外循环杂志,2007,5(1):54-56.
[49]Grigore AM,Grocott HP,Mathew JP,et al.The rewarming rate and increased peak temperature alter neurocognitive outcome after cardiac surgery.Anesth Analg,2002,94(l):4-10.
[50]Edmonds CR,Barbut D,Hager D,et al.Intraoperative cerebral arterial embolization during total hip arthroplasty.Anesthesiology,2000,93(2):315-318.
[51]Bickel H,Gradinger R,Kochs E,et al.Incidence and risk factors of delirium after hip surgery.Psychiatr Prax,2004 Oct,31(7):360-365.
[52]SoRelle R.Fever after coronary artery bypass graft surgery increases likelihood of cognitive loss.Circulation,2002 Feb 12,105(6):e9073-4.
[53]Grocott HP.Hyperglycemia and postoperative cognitive dysfunction:another call for better glycemic control? Can J Anaesth,2008 Mar,55(3):140-5.
[54]Veliz-Reissmiiller G,Agiiero Torres H,et al.Pre-operative mild cognitive dysfunction predicts risk for post-operative delirium after elective cardiac surgery.Aging Clin Exp Res,2007 Jun,19(3):172-7.
[55]Fearn SJ,Pole R,Wesnes K,et al.Cerebral injury during cardio-pulmonary bypass:emboli impair memory.J Thorac Cardiovasc Surg,2001,121(6):1150-1160.
[56]Robert P.Understanding and managing behavioural symptoms in Alzheimer's disease and related dementias:focus on rivastigmine.Curr Med Res Opin,2002,18(3):156-71.
[57]Narahashi T,Marszalec W,Moriguchi S,et al.Unique mechanism of action of Alzheimer's drugs on brain nicotinic acetylcholine receptors and NMDA receptors.Life Sci,2003 Dec 5,74(2-3):281-91.
[58]李茂全,王艳艳,余争平.糖皮质激素对海马功能损伤机制的研究进展.重庆医学,2006,35(12):1124-26.
[59]Wang D,Wu X,Li J,et al.The effect of lidocaine on early postoperative cognitive dysfunction after coronary artery bypass surgery.Anesth Analg,2002Nov,95(5):1134-41,table of contents.
[60]王东信,吴新民,李军,等.利多卡因对心脏手术后病人早期认知功能障碍发生率的影响.中华麻醉学杂志,2004,24(2):85-88.
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