大黄酸对糖尿病大鼠合并非酒精性脂肪性肝病的保护作用研究

The Hepatoprotective Effect of Rhein on Diabetic Rats with Non-alcoholic Fatty Liver Disease

[目的]观察大黄酸对糖尿病大鼠合并非酒精性脂肪性肝病(Non-alcoholic fatty liver disease,NAFLD)的肝脏保护作用并探讨其可能的机制。[方法]运用链脲佐菌素诱导高脂饲养的SD大鼠,将造模成功的糖尿病大鼠随机分为糖尿病模型组、吡格列酮组、大黄酸低、中、高剂量组,并以正常组作为对照。连续给药8周后分别测定各组大鼠的体质量(Body weight,BW)、肝湿重(liver weight,LW)、血谷丙转氨酶(Alanine aminotransferase,ALT)、谷草转氨酶(Aspartate aminotransferase,AST)、甘油三酯(Triglyceride,TG)、胆固醇(Cholesterol,TC)、空腹血糖(Fasting plasma glucose,FPG)、空腹胰岛素(Fasting insulin,FINS),计算肝脏肥大指数(Liver hypertrophy index,LW/BW)、胰岛素抵抗指数(Insulin resistance index,HOMA-IR),并观察肝脏组织病理变化。[结果]与正常对照组比较,糖尿病模型组大鼠LW、LW/BW、ALT、AST、TG、TC、FPG、FINS、HOMA-IR均明显升高(P<0.01),与糖尿病模型组比较,吡格列酮组和大黄酸低、中、高剂量组大鼠FINS、HOMA-IR明显降低,大黄酸高剂量组大鼠ALT、AST、TC均降低(P<0.05),并且TG、FPG、FINS、HOMA-IR明显降低(P<0.01);ALT与LW/BW、TC、HOMA-IR呈正相关,AST与LW/BW、TC呈正相关;光镜下糖尿病模型组大鼠肝小叶结构紊乱,呈严重的肝细胞脂肪变性,伴肝小叶炎性细胞浸润,吡格列酮组及大黄酸高剂量组大鼠肝脏脂肪变性明显改善,肝小叶炎症程度减轻。[结论]大黄酸对糖尿病大鼠具有肝脏保护作用,其机制可能与改善胰岛素抵抗有关。

[Objective] To observe the hepatoprotective effect of Rhein on diabetic rats with NAFLD,and to explore its possible mechanism.[Methods] Use streptozotocin-induced SD rats,fed with a high-fat diet.The modeling rats were randomly divided into diabetic model group,pioglitazone group,low,medium and high dose of R hein groups and the normal group as control.After they were continuously administered for eight weeks,BW,LW,ALT,AST,TG,TC,FPG,FINS,LW/BW,HOMA-IR were measured,and livers＇ histopathological changes were observed.[Results] Compared with normal control group,the model group had higher level of LW,LW/BW,ALT,AST,TG,TC,FPG,FINS,HOMA-IR（P〈0.01）; compared with diabetic model group,FINS,HOMA-IR were significantly lower in pioglitazone and low,medium dose of Rhein groups; high dose of R hein group had lower levels ofALT,AST,TC（P〈0.05）,and also significantly lower levels ofTG,FPG,FINS,HOMA-IR（P〈0.01）; ALT was positively correlated to LW/BW,TC,HOMA-IR; AST was positively correlated to LW/BW and TC; the morphological study showed that the liver lobular structure disorder,hepatic steatosis and inflammatory cell infiltration were severe in diabetic model group; hepatic steatosis and lobular inflammation were significantly ameliorated in pioglitazone and high dose of Rhein group.[Conclusion] R hein has hepatoprotective effect on diabetic rats,its mechanism may be related to the improvement of insulin resistance.