c-Jun氨基末端激酶信号通路对肥胖诱导的大鼠胰岛β细胞凋亡的调控作用

Regulatory effects of c-Jun N-terminal kinase signaling pathway on islet β-cell apoptosis induced by obesity

目的探讨c-Jun氨基末端激酶（JNK）信号通路对肥胖诱导的大鼠胰岛B细胞凋亡的调控作用。方法采用高脂饲料喂养雄性SD大鼠建立肥胖模型。造模成功后，取对照组和肥胖组大鼠各10只，检测其空腹血糖、游离脂肪酸及血清胰岛素水平，计算胰岛素抵抗指数。观察其胰腺组织病理学变化，并检测其胰腺组织中胰岛素、胰岛细胞凋亡指数及胰腺组织肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β、磷酸化JNK（p-JNK）、B细胞淋巴瘤／白血病-2（Bcl-2）和Bcl-2相关X蛋白（Bax）的表达水平。结果肥胖组大鼠胰腺组织出现腺泡结构破坏、脂质块状沉积等病理学改变。肥胖组大鼠空腹血糖、游离脂肪酸、血清胰岛素、胰岛素抵抗指数、B细胞凋亡指数、TNF-β、IL-1β、胰腺组织中胰岛素、P-JNK、Bax的表达水平显著高于对照组（P均〈0．05）；而Bcl-2表达水平显著低于对照组（P〈0．05）。结论JNK信号通路在肥胖大鼠被激活，进而发挥促肥胖诱导的大鼠胰岛β细胞凋亡的作用。

Objective -To investigate the regulatory effects of c-Jun N-terminal kinase （JNK） signaling pathway on islet β-cell apoptosis induced by obesity. Methods Male SD rats were selected to establish obese models by feeding high fat diet. Rats in normal control group（ n = 10） and obese model group（ n = 10 ）were picked out for testing. The levels of fasting plasma glucose （FPG） , free fatty acids （FFA）, serum fasting insulin （FINS） were measured and insulin resistance index （HOMA-IR） was calculated. The pathological changes of pancreatic tissues were observed. FINS in pancreatic tissues, apoptotic index in pancreatic cells and tmnor necrosis factor （TNF） -α, interleukin （IL） - 1β, phosphorylated c-jun N-terminal kinase （p-JNK）, B cell lymphoma/lewkmia-2 （Bcl-2） and Bcl-2 relaed X protein in pancreatic tissves Bax in pancreatic tissues were tested. Results The structure of pancreatic acinus were damaged, and there were obvious lipid deposition inpancreatie tissues. Compared with normal control group, the levels of FPG, FFA, FINS, HOMA-IR, apoptotic index of β cells, TNF-α, IL-1β, p-JNK and Bax significantly increased and the level of Bcl-2 profoundly decreased in obese model group （ P 〈 0.05 ）. Conclusion JNK signaling pathway was activated in the obese rats, and then played a positive role in the apoptosis of pancreatic β-cells.