邹雨桐　张智博　宋佩

[摘要] 目的 研究腎素-血管紧张素系统（RAS）在慢性应激诱导下的大鼠胰岛素分泌中所起作用。 方法 将20只SD大鼠随机分为4组，正常对照、电击组、卡托普利（captopril）处理加电击、坎地沙坦（candesartan）处理加电击。3个需要电击处理组连续电击4周，4组大鼠定期测量血压，在电击结束后行腹腔注射葡萄糖耐量（IPGTT）实验，在相应的时间点测定大鼠血糖水平，处死后收集血清和胰脏，测定血清中血管紧张素Ⅱ（angiotensin Ⅱ，Ang Ⅱ）和胰岛素水平，用Q-PCR测定各组大鼠的Pcsk1基因和Pcsk2基因的表达情况。 结果 在慢性应激情况下，只经电击处理的大鼠血压和血清血管紧张素Ⅱ水平均高于对照组大鼠的正常水平（P<0.05）；分别经过血管紧张素Ⅱ受体（AT1）拮抗剂-坎地沙坦（candesartan）和血管紧张素转化酶抑制剂-卡托普利（captopril）处理的两个组，大鼠的血压及Ang Ⅱ水平均低于对照组水平（P<0.05）。3组电击处理过的大鼠血清胰岛素水平均明显低于对照组（P<0.05）。电击4周后的IPGTT显示，4组大鼠的糖耐量水平表现无显著差异。3个电击处理组大鼠Pcsk1基因的表达相比对照组明显降低（P<0.05），各组大鼠Pcsk2基因表达无明显差异。 结论 在慢性应激4周的情况下，大鼠胰岛素分泌出现显著下降，卡托普利（captopril）和坎地沙坦（candesartan）处理并未改善慢性应激诱导引起的胰岛素分泌下降，因此，RAS系统可能未参与慢性应激诱导的胰岛素分泌下降。

[关键词] 肾素-血管紧张素系统（RAS）；应激；胰岛素；糖尿病

[中图分类号] R587.1 [文献标识码] A [文章编号] 1673-9701（2018）20-0036-05

The role of renin-angiotensin system（RAS） in insulin secretion under chronic stress

ZOU Yutong1 ZHANG Zhibo1 SONG Pei1 XU Qun1 ZHANG Guoxing2

1.The First School of Clinical Medicine， Suzhou University School of Medicine， Suzhou 215123， China； 2.Faculty of Physiology， School of Basic Medicine and Life Sciences， Suzhou University School of Medicine， Suzhou 215123， China

[Abstract] Objective To study the role of renin-angiotensin system（RAS） in the insulin secretion of rats induced by chronic stress. Methods 20 SD rats were randomly divided into 4 groups： a normal control group， a shock group， captopril treatment plus electric shock， and candesartan treatment plus electric shock. Three groups which needed electric shocks were given electric shock for 4 weeks consecutively. Four groups of rats were regularly given measurement of blood pressure. At the end of the shock， an intraperitoneal glucose tolerance test（IPGTT） was performed. The rats' blood glucose levels were measured at the corresponding time points. Serum and pancreas were collected after sacrifice. The serum angiotensin Ⅱ（Ang Ⅱ） and insulin levels were measured， and the expression of Pcsk1 gene and Pcsk2 gene in each group of rats was determined by Q-PCR. Results Under chronic stress conditions， the blood pressure and serum angiotensin Ⅱ levels in rats treated with electroshock were higher than the normal levels in the rats from the control group（P<0.05）； in group treated with angiotensin Ⅱ receptor（AT1） antagonists-candesartan and angiotensin converting enzyme inhibitor-captopril respectively， the blood pressure and Ang Ⅱ levels in rats were lower than those in the control group（P<0.05）. The serum insulin levels in rats treated with electroshock in the three groups were significantly lower than those in the control group（P<0.05）. IPGTT after 4 weeks of electroshock showed no significant difference in glucose tolerance levels between the four groups. Compared with the control group， the expression of Pcsk1 gene in the three electroshock groups was significantly lower（P<0.05）. There was no significant difference in the expression of Pcsk2 gene between all groups. Conclusion In the case of chronic stress for 4 weeks， insulin secretion is significantly reduced in rats. Treatment with captopril and candesartan do not improve the reduction of insulin secretion induced by chronic stress induction. Therefore， RAS system may not be involved in the chronic stress-induced decrease in insulin secretion.

[Key words] Renin-angiotensin system（RAS）； Stress； Insulin； Diabetes

近40年来，我国经济社会发展迅猛，人口老龄化趋势明显，糖尿病等多发生于老年人群的代谢性疾病发病率呈现出显著增高的趋势，当前我国统计的数据显示，国内现有15.5%患有糖尿病[1]。2型糖尿病（type 2 diabetes mellitus，T2DM）作为一种临床常见的糖尿病类型，是以胰岛 B细胞功能缺陷和胰岛素抵抗为主要病理生理改变的代谢性疾病，目前认为由遗传和环境因素互相作用引起。胰岛素抵抗（insulin resistance，IR）和胰岛 B细胞功能缺陷在糖尿病的发展过程中扮演重要角色[2]。胰岛素抵抗是机体对一定量或浓度的胰岛素的生物效应减低，主要指机体由胰岛素介导的葡萄糖摄取和代谢能力减弱，包括胰岛素的敏感性下降和反应性下降[3]。有关T2DM胰岛素抵抗的发生机制比较复杂，一直是研究的热点。……