血管紧张素(1-7)对糖尿病大鼠胰岛素抵抗的影响及机制研究  

The effects and mechanism of angiotensin-(1-7)on insulin resistance in diabetic rats

作　　者：王瑞娇 王巍[1] 郭红[1] 程海华 何军华[1] WANG Ruijiao;WANG Wei;GUO Hong(Department of Endocrinology,The Second Hospital of Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学第二医院内分泌科,太原030001

出　　处：《中国糖尿病杂志》2021年第4期293-299,共7页Chinese Journal of Diabetes

基　　金：山西省自然科学基金(201901D111374);山西省回国留学人员科研资助项目(2017-117);山西省卫生健康委科研项目(2019041)。

摘　　要：目的探讨血管紧张素(1-7)[Ang-(1-7)]对DM大鼠IR的影响及可能机制。方法随机选取Wistar大鼠10只为正常对照组(NC),另取24只予高脂饮食喂养联合STZ注射构建DM模型,造模成功的20只大鼠随机分为糖尿病组(DM)、Ang-(1-7)组[Ang-(1-7)300μg/(kg.d)皮下注射],每组各10只。干预8周后检测FPG、FIns及血管紧张素II(Ang II)水平,计算稳态模型胰岛素抵抗指数(HOMA-IR)及敏感指数(HOMA-ISI),观察肝脏病理改变,检测肝脏炎症通路及Ins信号转导通路相关因子的mRNA及蛋白表达。结果与NC组比较,DM、Ang-(1-7)组体重、FIns、HOMA-ISI、IRS-2 mRNA、磷脂酰肌醇3激酶(PI3K)mRNA和蛋白、丝氨酸/苏氨酸蛋白激酶2(Akt-2)mRNA和蛋白表达降低(P<0.05),FPG、Ang II、HOMA-IR、肝脏指数、IκB激酶β(IKKβ)mRNA和蛋白、核因子κB(NF-κB)mRNA和蛋白、TNF-αmRNA、IL-6 mRNA、糖原合成酶激酶3α(GSK-3α)mRNA和蛋白表达升高(P<0.05)。与DM组比较,Ang-(1-7)组FPG、Ang II、HOMA-IR、肝脏指数、IKKβmRNA和蛋白、NF-κB mRNA和蛋白、TNF-αmRNA、IL-6 mRNA、GSK-3αmRNA和蛋白表达降低,FIns、HOMA-ISI、IRS-2 mRNA、PI3K m RNA和蛋白、Akt-2 mRNA和蛋白表达升高(P<0.05)。结论Ang-(1-7)可能通过抑制肝脏IKKβ/NF-κB炎症通路及上调IRS-2/PI3K/Akt-2胰岛素信号通路,改善IR。Objective To explore the effect of angiotensin-(1-7)on improving of insulin resistance(IR)in diabetic rats and elucidate the underlying mechanism.selected as normal control group(NC)and fed with normal diet.The other 24 rats were induced via high-fat diet combined with intraperitoneal injection of low-dose streptozotocin(STZ)to establish diabetic rat model.20 successfully modeled rats were randomly divided into diabetes mellitus group(DM)and Ang-(1-7)group[Ang-(1-7)300μg/(kg·d)].After 8 weeks of intervention,fasting plasma glucose(FPG),serum angiotensin II(AngII)and fasting insulin(FIns)were measured.Homeostasis model assessment of insulin resistance(HOMA-IR)and insulin sensitivity index(HOMA-ISI)were calculated.The histomorphology of liver was evaluated by HE staining.The mRNA and protein expressions of the inflammation pathway and insulin signaling pathway were measured by real-time PCR and immunohistochemistry analysis.pared with NC group,body weight,FIns,HOMA-ISI,insulin receptor substrate 2(IRS-2)mRNA and protein,phosphatidylinositol-3-kinase(PI3 K)mRNA and protein,serine threonine protein kinase 2(Akt-2)mRNA and protein expressions in DM and Ang-(1-7)groups decreased(P<0.05).The levels of FPG,Ang II,HOMA-IR,liver index and the expressions of IκB kinaseβ(IKKβ)mRNA and protein,nuclear factorκB(NF-κB)mRNA and protein,TNF-αmRNA,IL-6 mRNA,glycogen synthase kinase 3α(GSK-3α)mRNA and protein increased(P<0.05).Compared with DM group,the levels of FPG,Ang II,HOMA-IR,liver index and the expressions of IKKβmRNA and protein,NF-κB mRNA and protein,TNF-αm RNA,IL-6 mRNA,GSK-3αmRNA and protein decreased in Ang-(1-7)group(P<0.05).The levels of FIns,HOMA-ISI,IRS-2 mRNA and the expressions of PI3 K mRNA and protein,Akt-2 mRNA and protein increased(P<0.05).Conclusion Ang-(1-7)may improve insulin resistance by inhibiting IKKβ/NF-κB inflammation pathway and upregulating IRS-2/PI3 K/Akt-2 signaling pathway.

关 键 词：血管紧张素(1-7) IκB激酶β/核因子κB 胰岛素受体底物2/磷脂酰肌醇3激酶/丝氨酸/苏氨酸蛋白激酶2 胰岛素抵抗 

分 类 号：R587.1[医药卫生—内分泌]