高脂血症对大鼠重症急性胰腺炎的影响及其机制研究
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摘要
目的:观察高脂血症对大鼠重症急性胰腺炎严重程度的影响;过氧化物酶增殖物激活受体γ(peroxisome proliferater-activated receptor gamma, PPAR-γ)在重症急性胰腺炎和重症急性胰腺炎伴有高脂血症中的表达差异,初步探讨高脂血症影响重症急性胰腺炎炎症程度的发病机制。
方法: 40只健康雄性Sprague-Dawley大鼠,体重120-150g,随机分为4组:正常对照组(C组)10只,重症急性胰腺炎组(SAP组)10只,高脂血症组(TG组)10只,重症急性胰腺炎伴有高脂血症组(SAP-TG组)10只。C组和SAP组普通饲料喂养,SAP组和SAP-TG组高脂饲料喂养。4周后C组及TG组,腹主动脉采血送协和武汉协和医院用AEROSET全自动生化分析仪行甘油三脂检查,取胰腺及肺脏组织匀浆,RT-PCR法测PPAR-γ的表达。AP组及AP-TG组禁食12h后制作重症急性胰腺炎模型,6小时后腹主动脉采血进行丙二醛(malondialdehyde,MDA)检测;干纱布蘸取腹水测腹水量%(腹水重量g/体重g×100%);取胰腺部分组织及肺脏匀浆,RT-PCR测PPAR-γ的表达;并取胰腺组织10%中性甲醛固定送病理检查,常规HE染色。胰腺病理组织评分采用Schmidt法。
结果:1血脂变化:高脂饲料喂养4周后,TG组大鼠甘油三脂水平明显升高,达1.68±0.21 mmol/,明显高于正常对照组,差异有显著性(P<0.05)2、胰腺及肺脏组织PPAR-γ表达:与C组相较,TG组及AP组PPAR-γ表达均升高,差异有显著性(P<0.05);与SAP组相比,SAP-TG组PPAR-γ表达含量下降,差异有显著性(P<0.05);3.MDA含量:与SAP组相比,SAP-TG组MDA含量明显升高,达2.321±0.241ummol/L,差异有显著性(p<0.05);4、胰腺腹水量(%):与SAP组相比,SAP-TG组胰腺腹水量(%)升高,分别为11.624±2.009%vs15.800±1.046%,差异有显著性(p<0.05)5.病理评分:与SAP组相比,SAP-TG组各项炎症病理评分明显升高,差异有显著性(p<0.05)。
结论:1.高脂血症可以加重重症急性胰腺炎炎症程度2.PPAR-γ降低可能是高脂血症加重重症急性胰腺炎炎症程度的原因之一
Objective: To investigate the influence of hyperlipemia in severe acute pancreatitis SAP, the expressinn of Peroxisome Proliferater Activated Receptor Gamma(PPAR-γ) and to discuss its significance in rats with SAP and SAP associate with hyperlipemia.
Methods: 40 healthy male Sprague-Dawley rats, weighing 120-150g. were randomly divided into four groups : control group (C group), acute pancreatitis group (SAP group,n=10;hyperlipidemia group (TG group.n=10), acute pancreatitis associated with hyperlipidemia group(SAP-TG group,n=10). SAP group and control group:balance feed for 4 weeks; TG group and SAP-TG group:high fat feed for 4 weeks.Four weeks later, control group and TG group were sacrificed. Blood sample, pancreatic tissues and lung tissues were collected.We used AEROSET automatic biochemical analyzer to inspection triglyceride.The expression of PPAR-γwas inspected by RT-PCR test. SAP modle was induced by injection of 5% sterile sodium taurocholate into biliopancreatic duct. Rats were sacrificed at 6 hours after the onset of operation.Blood sample and pancreatic tissues were collected and the expresion of MDA in blood was examined by TBA method ; Measuring the amount of ascites by dry gauze % (ascites weight g /body weight g×100%); With part of pancreatic tissues,PPAR-γexpression was detected by RT-PCR. We put pancreatic tissues in 10% neutral formalin-fixed and took pancreatic tissue sent for histopathologic examination,and HE staining. Schmidt scoring method was used to evaluate pancreatic pathology.
Results:1. lipid changes : After 4 weeks of high-fat diet, rats TG triglyceride levels were significantly increased. The difference was significant(P<0.05);2. PPAR-γexpression in pancreas and lung tissues: Compared with group C, expression of PPAR-gamma in group TG and group SAP were increased, the difference was significant (P <0.05); Compared with group SAP, expression of PPAR-γin group SAP-TG decreased,the difference was also significant (P<0.05);3. MDA content:Compared with group SAP, MDA content in group SAP-TG was significantly higher. The difference was significant (p <0.05);4.pancreatic ascites (%) : Compared with group SAP, pancreatic ascites (%) of group SAP-TG increased, the difference was significant (p <0.05);5. Pancreatic pathology grade : Compared with group SAP, inflammatory pathology scores of group SAP-TG increased significantly.The difference was significant (p <0.05).
Conclusion:1.Hyperlipemia can reduce the inflammation of acute pancreatitis.2.The decrease of PPAR-γmay be one of the reasons that hyperlipidemia add the inflammation of severe acute pancreatitis.
方法: 40只健康雄性Sprague-Dawley大鼠,体重120-150g,随机分为4组:正常对照组(C组)10只,重症急性胰腺炎组(SAP组)10只,高脂血症组(TG组)10只,重症急性胰腺炎伴有高脂血症组(SAP-TG组)10只。C组和SAP组普通饲料喂养,SAP组和SAP-TG组高脂饲料喂养。4周后C组及TG组,腹主动脉采血送协和武汉协和医院用AEROSET全自动生化分析仪行甘油三脂检查,取胰腺及肺脏组织匀浆,RT-PCR法测PPAR-γ的表达。AP组及AP-TG组禁食12h后制作重症急性胰腺炎模型,6小时后腹主动脉采血进行丙二醛(malondialdehyde,MDA)检测;干纱布蘸取腹水测腹水量%(腹水重量g/体重g×100%);取胰腺部分组织及肺脏匀浆,RT-PCR测PPAR-γ的表达;并取胰腺组织10%中性甲醛固定送病理检查,常规HE染色。胰腺病理组织评分采用Schmidt法。
结果:1血脂变化:高脂饲料喂养4周后,TG组大鼠甘油三脂水平明显升高,达1.68±0.21 mmol/,明显高于正常对照组,差异有显著性(P<0.05)2、胰腺及肺脏组织PPAR-γ表达:与C组相较,TG组及AP组PPAR-γ表达均升高,差异有显著性(P<0.05);与SAP组相比,SAP-TG组PPAR-γ表达含量下降,差异有显著性(P<0.05);3.MDA含量:与SAP组相比,SAP-TG组MDA含量明显升高,达2.321±0.241ummol/L,差异有显著性(p<0.05);4、胰腺腹水量(%):与SAP组相比,SAP-TG组胰腺腹水量(%)升高,分别为11.624±2.009%vs15.800±1.046%,差异有显著性(p<0.05)5.病理评分:与SAP组相比,SAP-TG组各项炎症病理评分明显升高,差异有显著性(p<0.05)。
结论:1.高脂血症可以加重重症急性胰腺炎炎症程度2.PPAR-γ降低可能是高脂血症加重重症急性胰腺炎炎症程度的原因之一
Objective: To investigate the influence of hyperlipemia in severe acute pancreatitis SAP, the expressinn of Peroxisome Proliferater Activated Receptor Gamma(PPAR-γ) and to discuss its significance in rats with SAP and SAP associate with hyperlipemia.
Methods: 40 healthy male Sprague-Dawley rats, weighing 120-150g. were randomly divided into four groups : control group (C group), acute pancreatitis group (SAP group,n=10;hyperlipidemia group (TG group.n=10), acute pancreatitis associated with hyperlipidemia group(SAP-TG group,n=10). SAP group and control group:balance feed for 4 weeks; TG group and SAP-TG group:high fat feed for 4 weeks.Four weeks later, control group and TG group were sacrificed. Blood sample, pancreatic tissues and lung tissues were collected.We used AEROSET automatic biochemical analyzer to inspection triglyceride.The expression of PPAR-γwas inspected by RT-PCR test. SAP modle was induced by injection of 5% sterile sodium taurocholate into biliopancreatic duct. Rats were sacrificed at 6 hours after the onset of operation.Blood sample and pancreatic tissues were collected and the expresion of MDA in blood was examined by TBA method ; Measuring the amount of ascites by dry gauze % (ascites weight g /body weight g×100%); With part of pancreatic tissues,PPAR-γexpression was detected by RT-PCR. We put pancreatic tissues in 10% neutral formalin-fixed and took pancreatic tissue sent for histopathologic examination,and HE staining. Schmidt scoring method was used to evaluate pancreatic pathology.
Results:1. lipid changes : After 4 weeks of high-fat diet, rats TG triglyceride levels were significantly increased. The difference was significant(P<0.05);2. PPAR-γexpression in pancreas and lung tissues: Compared with group C, expression of PPAR-gamma in group TG and group SAP were increased, the difference was significant (P <0.05); Compared with group SAP, expression of PPAR-γin group SAP-TG decreased,the difference was also significant (P<0.05);3. MDA content:Compared with group SAP, MDA content in group SAP-TG was significantly higher. The difference was significant (p <0.05);4.pancreatic ascites (%) : Compared with group SAP, pancreatic ascites (%) of group SAP-TG increased, the difference was significant (p <0.05);5. Pancreatic pathology grade : Compared with group SAP, inflammatory pathology scores of group SAP-TG increased significantly.The difference was significant (p <0.05).
Conclusion:1.Hyperlipemia can reduce the inflammation of acute pancreatitis.2.The decrease of PPAR-γmay be one of the reasons that hyperlipidemia add the inflammation of severe acute pancreatitis.
引文
1. Fortson MR, Freedman SN, Webster PD.Clinical assessment of hyperlipidemic pancreatitis. Am J Gastroenterol 1995;90:2134-9
2. Rollins MD,Sudarshan S,Firpo MA et al Anti-inflammatory effects of PPAR-gamma agonists directly correlate with PPAR-gamma expression during acute pancreatitis.J Gastrointest Surg. 2006 Sep-Oct;10(8):1120-30
3. YQ Li, YJ Gao, LY Huang. The clinical features of acute pancreatitis in 10 cities in Shandong Province. Zhonghua Nei Ke Za Zhi, September 1, 2004; 43(9): 672-4
4. Miller A, Lees RS, McCluskey MA, et al. The natural history and surgical significance of hyperlipemic abdominal crisis. Ann Surg 1979;190:401–8.
5. Greenberg BH, Blackwelder WC, Levy RL. Primary type-V hyperlipoproteinemia. A descriptive study in 32 families. Ann Intern Med 1977;87:526–34.
6. Nagai H,Henrich H,Wunsch P,et al. Role of pancreatic enzymes and their substrates in autodigestion of the pancreas:in vivo studies with isolated rat pancreatic acini [J]. Gastroenterology,1989,96(3):838-847.32. Domschke S, et al. Int J Pancreatol 1993; 13(2): 105-110
7. M aria A,M artinez,Ana I,et a1.Diatary virgin olive oil an hances seeretagogue evoked calcium signaling in rat pancreatic aeinar cells.Nutritional,2004;20:536-54
8. Genovese T,Mazzon E,Di Paola R et al. Role of peroxisome proliferator-activated receptor-alpha in acute pancreatitis induced by cerulein. Immunology 2006 Aug;118 (4):559-70. Epub 2006 Jun 8
9. Emma Folch-Puy, Susana Granell, Juan L Iovanna, Marc Barthet, Daniel Closa. Peroxisome proliferator-activated receptorγagonist reduces the severity of post-ERCP pancreatitis in rats. World J Gastroenterol 2006 October 28; 12(40): 6458-6463
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2. Rollins MD,Sudarshan S,Firpo MA et al Anti-inflammatory effects of PPAR-gamma agonists directly correlate with PPAR-gamma expression during acute pancreatitis.JGastrointest Surg. 2006 Sep-Oct;10(8):1120-30
3. Genovese T, Mazzon E, Di Paola R.et al. Role of peroxisome proliferator-activated receptor-alpha in acute pancreatitis induced by cerulein. Immunolgy ,2006 Aug;118(4):559-70. Epub 2006 Jun 8
4. Emma Folch-Puy, Susana Granell, Juan L Iovanna, Marc Barthet, Daniel Closa. Peroxisome proliferator-activated receptorγagonist reduces the severity of post-ERCP pancreatitis in rats. World J Gastroenterol 2006 October 28; 12(40): 6458-6463
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2. Rollins MD,Sudarshan S,Firpo MA et al Anti-inflammatory effects of PPAR-gamma agonists directly correlate with PPAR-gamma expression during acute pancreatitis.J Gastrointest Surg. 2006 Sep-Oct;10(8):1120-30
3. YQ Li, YJ Gao, LY Huang. The clinical features of acute pancreatitis in 10 cities in Shandong Province. Zhonghua Nei Ke Za Zhi, September 1, 2004; 43(9): 672-4
4. Miller A, Lees RS, McCluskey MA, et al. The natural history and surgical significance of hyperlipemic abdominal crisis. Ann Surg 1979;190:401–8.
5. Greenberg BH, Blackwelder WC, Levy RL. Primary type-V hyperlipoproteinemia. A descriptive study in 32 families. Ann Intern Med 1977;87:526–34.
6. Nagai H,Henrich H,Wunsch P,et al. Role of pancreatic enzymes and their substrates in autodigestion of the pancreas:in vivo studies with isolated rat pancreatic acini [J]. Gastroenterology,1989,96(3):838-847.32. Domschke S, et al. Int J Pancreatol 1993; 13(2): 105-110
7. M aria A,M artinez,Ana I,et a1.Diatary virgin olive oil an hances seeretagogue evoked calcium signaling in rat pancreatic aeinar cells.Nutritional,2004;20:536-54
8. Genovese T,Mazzon E,Di Paola R et al. Role of peroxisome proliferator-activated receptor-alpha in acute pancreatitis induced by cerulein. Immunology 2006 Aug;118 (4):559-70. Epub 2006 Jun 8
9. Emma Folch-Puy, Susana Granell, Juan L Iovanna, Marc Barthet, Daniel Closa. Peroxisome proliferator-activated receptorγagonist reduces the severity of post-ERCP pancreatitis in rats. World J Gastroenterol 2006 October 28; 12(40): 6458-6463
1. Fortson MR, Freedman SN, Webster PD . Clinical assessment of hyperlipidemic pancreatitis. Am J Gastroenterol 1995;90:2134-9
2. Rollins MD,Sudarshan S,Firpo MA et al Anti-inflammatory effects of PPAR-gamma agonists directly correlate with PPAR-gamma expression during acute pancreatitis.JGastrointest Surg. 2006 Sep-Oct;10(8):1120-30
3. Genovese T, Mazzon E, Di Paola R.et al. Role of peroxisome proliferator-activated receptor-alpha in acute pancreatitis induced by cerulein. Immunolgy ,2006 Aug;118(4):559-70. Epub 2006 Jun 8
4. Emma Folch-Puy, Susana Granell, Juan L Iovanna, Marc Barthet, Daniel Closa. Peroxisome proliferator-activated receptorγagonist reduces the severity of post-ERCP pancreatitis in rats. World J Gastroenterol 2006 October 28; 12(40): 6458-6463
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