非酒精性脂肪性肝炎的发病机制研究进展
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摘要
近年来,随着国内生活水平的提高,非酒精性脂肪性肝炎(Nonalcoholic Steatohepatitis,NASH)的发病率日益升高。NASH本身可影响其他慢性肝病进展,并与代谢综合征的发病互为因果。由于目前其发病机制尚不明确,故缺乏有效防治措施。文章对国内外近5年来的主要文献进行整理,对NASH发病机制的认识及研究进展做一综述。
In recent years,with the improvement of living standards,the incidence of non-alcoholic steatohepatitis( NASH) is increasing. NASH may affect the progression of others chronic liver disease. NASH and metabolic syndrome interact with each other.As the pathogenesis is still poorly understood,there is no effective prevention and control measures so far. In this paper,the main literature in China and abroad during the past five years was collected and understanding and the development research of NASH's pathogenesis were reviewed.
In recent years,with the improvement of living standards,the incidence of non-alcoholic steatohepatitis( NASH) is increasing. NASH may affect the progression of others chronic liver disease. NASH and metabolic syndrome interact with each other.As the pathogenesis is still poorly understood,there is no effective prevention and control measures so far. In this paper,the main literature in China and abroad during the past five years was collected and understanding and the development research of NASH's pathogenesis were reviewed.
引文
[1]郑昕,王亚平,张志银,等.基于“体质可调”理论治疗非酒精性脂肪性肝炎临床研究[J].世界中医药,2014,9(3):308-310.
[2]王金周.自拟消脂方治疗非酒精性脂肪性肝炎的42例临床观察[J].世界中医药,2013,8(7):752-754.
[3]杜井峰,杨丽,朱艳丽,等.GHR、COG基因多态性与NASH发病关系的研究[J].齐齐哈尔医学院学报,2013,34(11):1561-1562.
[4]周光德,李美蓉,赵景民.环氧化酶-2在非酒精性脂肪性肝炎大鼠发病中的作用[J].中华消化病与影像杂志:电子版,2012,2(1):17-21.
[5]陈鸿,袁禧先,西原利治.CPTⅡ基因F352C多态性与非酒精性脂肪性肝炎易感性的研究[J].黑龙江医药科学,2011,34(1):6-7.
[6]梁衍锋,张东东,张晓波,等.AT1R基因A1166C多态性与非酒精性脂肪性肝炎关系的研究[J].黑龙江医药科学,2010,33(6):12-13.
[7]王晓敏,文倩,陈东风.核因子KLF6与PPARγ在大鼠非酒精性脂肪性肝炎中的动态变化[J].海南医学院学报,2012,18(4):452-456.
[8]张惠清,钟明康,张洁,等.非酒精性脂肪性肝炎大鼠肝细胞损伤与细胞间黏附分子-1表达的关系[J].上海交通大学学报:医学版,2009,29(5):517-520.
[9]Cianfarani S,Agostoni C,Bedogni G,et al.Effect of intrauterine growth retardation on liver and long-term metabolic risk[J].Int J Obes(Lond),2012,36(10):1270-1277.
[10]钟岚,范建高,王国良,等.非酒精性脂肪性肝炎发病机制的实验研究[J].中华消化杂志,2001,21(8):484.
[11]武彦宁,蔡照华,孙海梅,等.非酒精性脂肪性肝炎大鼠肝脏内源性H2S合成减少[J].首都医科大学学报,2010,31(3):287-292.
[12]刘亮,肖延风,尹春燕,等.内质网应激在高脂饲料诱导幼年大鼠脂肪性肝损伤中的作用[J].西安交通大学学报:医学版,2015,36(6):724-729.
[13]赖姝婕,王军,王斌,等.沉默PKCδ表达对L02肝细胞脂肪变性和内质网应激的影响[J].第三军医大学学报,2014,36(7):650-654.
[14]严红梅,刘林,孟培燕,等.非酒精性脂肪性肝炎大鼠肝脏细胞间黏附分子-1蛋白表达及杞蓟制剂对其影响的研究[J].中国实验方剂学杂志,2010,16(12):150-152.
[15]叶青,尹伟利,王凤梅,等.非酒精性脂肪性肝病患者血清s ICAM-1水平变化及意义[J].山东医药,2014,54(10):54-56.
[16]马红,郭春花,杨香玖.非酒精性脂肪性肝病患者肝脏脂联素的表达与病理改变的关系[J].中国老年学杂志,2014,34(16):4480-4482.
[17]朱超慧,陈东风,艾正琳,等.血清内脏脂肪素、脂联素与非酒精性脂肪性肝病临床病理的关系[J].临床肝胆病杂志,2011,27(7):735-748.
[18]钱晓武,范竹萍,邱德凯.脂联素及受体与非酒精性脂肪性肝炎[J].国际消化病杂志,2006,26(3):157-160.
[19]方文莉,施敏,魏珏,等.NALP3炎性体在小鼠非酒精性脂肪性肝炎发病中的作用[J].肝脏,2012,17(5):315-318.
[20]施敏,王玉刚,王霆,等.NOX1和NOX4在小鼠非酒精性脂肪性肝炎发病中的作用[J].实用临床医药杂志,2012,16(23):5-8.
[21]张宗胜.脂联素基因多态性与广东省普通人群非酒精性脂肪性肝病发病及自然病程相关性研究[D].广州:广州医学院,2012.
[22]杨林辉,蔡俊,刘国栋,等.非酒精性脂肪性肝炎患者肠道菌群失调与肠道通透性及血清内毒素的相关性研究[J].中国微生态学杂志,2012,24(9):801-804.
[23]卢伟娜.肠源性内毒素血症对NASH大鼠的影响及其作用机制的探讨[D].石家庄:河北医科大学,2010.
[24]沈颖娟.非酒精性脂肪性肝病大鼠肠源性内毒素血症与PPARa的关系的实验性研究[D].石家庄:河北医科大学,2012.
[25]张丽霞,刘近春,武雯,等.髓系细胞触发受体-1在非酒精性脂肪性肝炎中的作用[J].中西医结合肝病杂志,2011,21(6):356-358.
[26]秦涛.TREM-1、TREM-2在非酒精性脂肪性肝炎时肝组织表达的研究[D].太原:山西医科大学,2012.
[27]周鑫.肠源性内毒素血症在NAFLD、T2DM发病中的作用及其分子机制的研究[D].太原:山西医科大学,2012.
[28]杨文慧,赵和平.抵抗素mRNA在非酒精性脂肪性肝炎大鼠肝组织中的表达与定位[J].实用肝脏病杂志,2008,11(4):225-228.
[29]王昭月,卞兆连,方一,等.CCR2在非酒精性脂肪性肝炎中的表达及意义[J].肝脏,2015,20(5):376-380.
[30]邵小娟,张艳梅,魏艳玲,等.NASH患者脂肪组织巨噬细胞计数的变化[J].实用肝脏病杂志,2013,16(6):502-504.
[31]黄珊珊,马雄.非酒精性脂肪性肝炎患者肝内Ig M的表达及其免疫调控作用[J].肝脏,2013,18(4):216-233.
[32]刘先进,李民,张玲燕,等.Lyn酶在非酒精性脂肪性肝炎组织Kupffer细胞中的表达及意义[J].江苏医药,2014,40(21):2608-2610,封2.
[33]覃岭,王宇童.过表达apo A-Ⅰ对BEL-7402细胞内脂质堆积的影响[J].首都医科大学学报,2012,33(2):198-204.
[34]刘伟,马东林,刘文文,等.过表达apo A-I对小鼠非酒精性脂肪性肝炎作用的研究[J].中国组织化学与细胞化学杂志,2013,22(2):109-114.
[35]刘欣,韩德五,郭建红,等.内毒素在NASH发展为肝纤维化中的作用[J].山西医科大学学报,2010,41(6):488-491.
[36]窦艳,邱鹏,陈江伟.TLR4在非酒精性脂肪性肝炎的表达及意义[J].中国实验诊断学,2013,17(7):1243-1245.
[37]Compare D,Coccoli P,Rocco A,et al.Gut-liver axis:the impact of gut microbiota on non alcoholic fatty liver disease[J].Nutr Metab Cardiovasc Dis,2012,22(6):471-476.
[38]Ahmed Abu Shanab,Paul Scully,Orla Crosbie,et al.Small intestinal bacterial overgrowth in nonalcoholic steatohepatitis:association with toll-like receptor 4 expression and plasma levels of interleukin 8[J].Dig Dis Sci,2011,56(5):1524-1534.
[39]Law K,Brunt EM.Nonalcoholic fatty liver disease[J].Clin Liver Dis,2010,14(4):591-604.
[40]杨林辉,蔡俊,陈东风.非酒精性脂肪性肝炎患者肠道菌群的变化及意义[J].临床肝胆病杂志,2012,28(2):124-126.
[41]Stoll B,Puiman PJ,Cui L,et al.Continuous parenteral and enteral nutrition induces metabolic dysfunction in neonatal pigs.JPEN J Parenter Enteral Nutr[J].JPEN J Parenter Enteral Nutr,2012,36(5):538-550.
[42]Paizis G,Cooper ME,Schembri JM,et al.Up-regulation of components of the renin-angiotensin system in the bile duct-ligated rat liver[J].Gastroenterology,2002,123(5):1667-1676.
[43]Wei Y,Clark SE,Thyfault JP,et al.Oxidative stress-mediated mitochondrial dysfunction contributes to angiotensin II-induced nonalcoholic fatty liver disease in transgenic Ren2 rats[J].Am J Pathol,2009,174(4):1329-1337.
[44]Rong X,Li Y,Ebihara K,et al.Angiotensin II type 1 receptor-independent beneficial effects of telmisartan on dietary-induced obesity,insulin resistance and fatty liver in mice[J].Diabetologia,2010,53(8):1727-1731.
[45]Kuwashiro S,Terai S,Oishi T,et al.Telmisartan improves nonalcoholic steatohepatitis in medaka(Oryzias latipes)by reducing macrophage infiltration and fat accumulation[J].Cell Tissue Res,2011,344(1):125-134.
[46]张丙贵.非酒精性脂肪性肝纤维化小鼠肝组织中异常表达miRNAs的鉴定及功能研究[D].石家庄:河北医科大学,2014.
[2]王金周.自拟消脂方治疗非酒精性脂肪性肝炎的42例临床观察[J].世界中医药,2013,8(7):752-754.
[3]杜井峰,杨丽,朱艳丽,等.GHR、COG基因多态性与NASH发病关系的研究[J].齐齐哈尔医学院学报,2013,34(11):1561-1562.
[4]周光德,李美蓉,赵景民.环氧化酶-2在非酒精性脂肪性肝炎大鼠发病中的作用[J].中华消化病与影像杂志:电子版,2012,2(1):17-21.
[5]陈鸿,袁禧先,西原利治.CPTⅡ基因F352C多态性与非酒精性脂肪性肝炎易感性的研究[J].黑龙江医药科学,2011,34(1):6-7.
[6]梁衍锋,张东东,张晓波,等.AT1R基因A1166C多态性与非酒精性脂肪性肝炎关系的研究[J].黑龙江医药科学,2010,33(6):12-13.
[7]王晓敏,文倩,陈东风.核因子KLF6与PPARγ在大鼠非酒精性脂肪性肝炎中的动态变化[J].海南医学院学报,2012,18(4):452-456.
[8]张惠清,钟明康,张洁,等.非酒精性脂肪性肝炎大鼠肝细胞损伤与细胞间黏附分子-1表达的关系[J].上海交通大学学报:医学版,2009,29(5):517-520.
[9]Cianfarani S,Agostoni C,Bedogni G,et al.Effect of intrauterine growth retardation on liver and long-term metabolic risk[J].Int J Obes(Lond),2012,36(10):1270-1277.
[10]钟岚,范建高,王国良,等.非酒精性脂肪性肝炎发病机制的实验研究[J].中华消化杂志,2001,21(8):484.
[11]武彦宁,蔡照华,孙海梅,等.非酒精性脂肪性肝炎大鼠肝脏内源性H2S合成减少[J].首都医科大学学报,2010,31(3):287-292.
[12]刘亮,肖延风,尹春燕,等.内质网应激在高脂饲料诱导幼年大鼠脂肪性肝损伤中的作用[J].西安交通大学学报:医学版,2015,36(6):724-729.
[13]赖姝婕,王军,王斌,等.沉默PKCδ表达对L02肝细胞脂肪变性和内质网应激的影响[J].第三军医大学学报,2014,36(7):650-654.
[14]严红梅,刘林,孟培燕,等.非酒精性脂肪性肝炎大鼠肝脏细胞间黏附分子-1蛋白表达及杞蓟制剂对其影响的研究[J].中国实验方剂学杂志,2010,16(12):150-152.
[15]叶青,尹伟利,王凤梅,等.非酒精性脂肪性肝病患者血清s ICAM-1水平变化及意义[J].山东医药,2014,54(10):54-56.
[16]马红,郭春花,杨香玖.非酒精性脂肪性肝病患者肝脏脂联素的表达与病理改变的关系[J].中国老年学杂志,2014,34(16):4480-4482.
[17]朱超慧,陈东风,艾正琳,等.血清内脏脂肪素、脂联素与非酒精性脂肪性肝病临床病理的关系[J].临床肝胆病杂志,2011,27(7):735-748.
[18]钱晓武,范竹萍,邱德凯.脂联素及受体与非酒精性脂肪性肝炎[J].国际消化病杂志,2006,26(3):157-160.
[19]方文莉,施敏,魏珏,等.NALP3炎性体在小鼠非酒精性脂肪性肝炎发病中的作用[J].肝脏,2012,17(5):315-318.
[20]施敏,王玉刚,王霆,等.NOX1和NOX4在小鼠非酒精性脂肪性肝炎发病中的作用[J].实用临床医药杂志,2012,16(23):5-8.
[21]张宗胜.脂联素基因多态性与广东省普通人群非酒精性脂肪性肝病发病及自然病程相关性研究[D].广州:广州医学院,2012.
[22]杨林辉,蔡俊,刘国栋,等.非酒精性脂肪性肝炎患者肠道菌群失调与肠道通透性及血清内毒素的相关性研究[J].中国微生态学杂志,2012,24(9):801-804.
[23]卢伟娜.肠源性内毒素血症对NASH大鼠的影响及其作用机制的探讨[D].石家庄:河北医科大学,2010.
[24]沈颖娟.非酒精性脂肪性肝病大鼠肠源性内毒素血症与PPARa的关系的实验性研究[D].石家庄:河北医科大学,2012.
[25]张丽霞,刘近春,武雯,等.髓系细胞触发受体-1在非酒精性脂肪性肝炎中的作用[J].中西医结合肝病杂志,2011,21(6):356-358.
[26]秦涛.TREM-1、TREM-2在非酒精性脂肪性肝炎时肝组织表达的研究[D].太原:山西医科大学,2012.
[27]周鑫.肠源性内毒素血症在NAFLD、T2DM发病中的作用及其分子机制的研究[D].太原:山西医科大学,2012.
[28]杨文慧,赵和平.抵抗素mRNA在非酒精性脂肪性肝炎大鼠肝组织中的表达与定位[J].实用肝脏病杂志,2008,11(4):225-228.
[29]王昭月,卞兆连,方一,等.CCR2在非酒精性脂肪性肝炎中的表达及意义[J].肝脏,2015,20(5):376-380.
[30]邵小娟,张艳梅,魏艳玲,等.NASH患者脂肪组织巨噬细胞计数的变化[J].实用肝脏病杂志,2013,16(6):502-504.
[31]黄珊珊,马雄.非酒精性脂肪性肝炎患者肝内Ig M的表达及其免疫调控作用[J].肝脏,2013,18(4):216-233.
[32]刘先进,李民,张玲燕,等.Lyn酶在非酒精性脂肪性肝炎组织Kupffer细胞中的表达及意义[J].江苏医药,2014,40(21):2608-2610,封2.
[33]覃岭,王宇童.过表达apo A-Ⅰ对BEL-7402细胞内脂质堆积的影响[J].首都医科大学学报,2012,33(2):198-204.
[34]刘伟,马东林,刘文文,等.过表达apo A-I对小鼠非酒精性脂肪性肝炎作用的研究[J].中国组织化学与细胞化学杂志,2013,22(2):109-114.
[35]刘欣,韩德五,郭建红,等.内毒素在NASH发展为肝纤维化中的作用[J].山西医科大学学报,2010,41(6):488-491.
[36]窦艳,邱鹏,陈江伟.TLR4在非酒精性脂肪性肝炎的表达及意义[J].中国实验诊断学,2013,17(7):1243-1245.
[37]Compare D,Coccoli P,Rocco A,et al.Gut-liver axis:the impact of gut microbiota on non alcoholic fatty liver disease[J].Nutr Metab Cardiovasc Dis,2012,22(6):471-476.
[38]Ahmed Abu Shanab,Paul Scully,Orla Crosbie,et al.Small intestinal bacterial overgrowth in nonalcoholic steatohepatitis:association with toll-like receptor 4 expression and plasma levels of interleukin 8[J].Dig Dis Sci,2011,56(5):1524-1534.
[39]Law K,Brunt EM.Nonalcoholic fatty liver disease[J].Clin Liver Dis,2010,14(4):591-604.
[40]杨林辉,蔡俊,陈东风.非酒精性脂肪性肝炎患者肠道菌群的变化及意义[J].临床肝胆病杂志,2012,28(2):124-126.
[41]Stoll B,Puiman PJ,Cui L,et al.Continuous parenteral and enteral nutrition induces metabolic dysfunction in neonatal pigs.JPEN J Parenter Enteral Nutr[J].JPEN J Parenter Enteral Nutr,2012,36(5):538-550.
[42]Paizis G,Cooper ME,Schembri JM,et al.Up-regulation of components of the renin-angiotensin system in the bile duct-ligated rat liver[J].Gastroenterology,2002,123(5):1667-1676.
[43]Wei Y,Clark SE,Thyfault JP,et al.Oxidative stress-mediated mitochondrial dysfunction contributes to angiotensin II-induced nonalcoholic fatty liver disease in transgenic Ren2 rats[J].Am J Pathol,2009,174(4):1329-1337.
[44]Rong X,Li Y,Ebihara K,et al.Angiotensin II type 1 receptor-independent beneficial effects of telmisartan on dietary-induced obesity,insulin resistance and fatty liver in mice[J].Diabetologia,2010,53(8):1727-1731.
[45]Kuwashiro S,Terai S,Oishi T,et al.Telmisartan improves nonalcoholic steatohepatitis in medaka(Oryzias latipes)by reducing macrophage infiltration and fat accumulation[J].Cell Tissue Res,2011,344(1):125-134.
[46]张丙贵.非酒精性脂肪性肝纤维化小鼠肝组织中异常表达miRNAs的鉴定及功能研究[D].石家庄:河北医科大学,2014.