肥胖对胰岛β细胞凋亡的影响

Effects of Obesity on Islet β-Cell Apoptosis

目的探讨肥胖对胰岛β细胞凋亡的影响及其可能的机制。方法取雄性SD大鼠,采用高脂饮食喂养的方法建立大鼠肥胖模型。取肥胖模型组(obese model group,OM组)和正常对照组(normal control group,NC组)大鼠各10只检测。测定空腹血糖(FBG)、总胆固醇(TC)、三酰甘油(TG)、游离脂肪酸(FFA)及血清胰岛素(FIns)的水平,计算胰岛素抵抗指数(HOMA-IR)。苏木精-伊红染色观察胰腺组织病理变化;脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL)检测β细胞凋亡水平;Western blot检测细胞色素C(Cyt C)在线粒体、细胞质中的分布情况及活化的胱天蛋白酶-3(Caspase-3)的表达水平。结果与NC组比较,OM组大鼠FBG、TC、TG、FFA、FIns、HOMA-IR、凋亡指数、胞质Cyt C水平及活化的Caspase-3表达水平均明显升高;线粒体Cyt C水平明显降低(均P<0.05);胰腺组织出现结构破坏、脂质变性等改变。结论肥胖通过线粒体途径增加胰岛β细胞的凋亡水平。

Objective To investigate the effects of obesity on isletβ-cell apoptosis and the possible mechanisms.MethodsObese models were established in male SD rats by high fat diet.The rats in the obese model group(n=10)and the normal control group(n=10)were selected for detecting fasting blood glucose(FBG),total cholesterol(TC),triglyceride(TG),free fatty acids(FFA),fasting insulin(FIns)and calculating insulin resistance index(HOMA-IR).The pathological changes of the pancreatic tissues were observed by hematoxylin-eosin(HE)staining and the apoptotic isletβcells were measured by TdT-mediated dUTP-biotin nick end labeling(TUNEL)method.Cytochrome C(Cyt C)in mitochondria,cytoplasm and cleaved cysteine aspartate-specific protease-3(Caspase-3)in isletβcells were determined by Western blotting.Results The levels of FBG,TC,TG,FFA,FIns,HOMA-IR,apoptotic index and Cyt C in cytoplasm and cleaved Caspase-3 were significantly increased and the level of Cyt C in mitochondria was profoundly decreased in the obese model group as compared with the normal control group(all P<0.05).In the rats of the obese model group,the structure of pancreatic tissues was damaged,and there was obvious steatosis.Conclusion Obesity can increase the apoptotic level of isletβcells by activation of mitochondrial apoptotic pathway.