非酒精性脂肪性肝病大鼠胰腺分泌状态及胰岛素抵抗观察

Secretory status of pancreas and pathogenesis of insulin resistance in rat with nonalcoholic fatty liver disease

目的研究非酒精性脂肪性肝病(NAFLD)大鼠的胰岛分泌状态及胰岛素受体(IR)表达的动态变化。方法建立NAFLD大鼠模型,应用HE染色、免疫组化、ELISA等方法观察胰腺组织结构、分泌状态和IR的表达变化。结果模型大鼠胰腺组织结构及血糖水平无明显变化。血清胰岛素水平在造模后4周明显升高(P<0.01),而组织中胰岛素水平从6周开始增加(P<0.01),且主要分布于胰岛的中央部,并呈现出逐渐增加的趋势。组织中胰高血糖素水平从8周开始增加(P<0.01),于12周达高峰,而IR表达从6周开始明显减少(P<0.01),8周后趋于稳定。结论NAFLD大鼠胰岛素和胰高血糖素的总体表达水平呈上升趋势,但胰岛素在组织与血清中的表达并不完全一致,且IR表达量减少,这可能是NAFLD时发生胰岛素抵抗的重要原因之一。

Objective Rats with nonalcoholic fatty liver disease （NAFLD） were used to investigate the secretory state of pancreas and the expression of insulin receptor （IR）. Methods NAFLD rat model was reproduced, and then the structure of pancreatic tissue, secretory states of α and β cells （serum, tissue） and the expression of IR were examined and determined by means of HE staining, ELISA, and immunohistochemistry. Results In all experimental groups, the structure of pancreatic tissue showed no obvious change; the blood sugar level tended to rise. The insulin level in serum began to elevate obviously at 4th week （P≤0.01）, while the insulin content in tissue began to increase at 6th week （P≤0.01）, and distributed mainly in the middle part of the pancreas with a tendency of elevation along with the time. The content of glucagon in pancreatic tissue began to increase at 8th week （P≤0.01）, and reached the peak at 12th week. The expression of IR in tissue began to decrease at 6th week （P≤0.01）, and then tended to be stable after 8th week. Conclusions In NAFLD, there was changes in secretory state of pancreas with the accompaniment of insulin resistance. There was a tendency of elevation of levels of insulin both in serum and pancreatic tissue, but the time of expression was different. The expression of glucagen shows an increase tendency, while the decrease of IR might be the crucial cause of insulin resistance in NAFLD.