芍药苷-6′-O-苯磺酸酯对胰岛素抵抗HASMC作用及机制  

Effect of paeoniflorin-6′-O-benzenesulfonate on HASMC with insulin resistance

作　　者：苏扬妮 黄琼芳 赵天娇 黄琼[1] 魏伟[1] Su Yangni;Huang Qiongfang;Zhao Tianjiao(Institute of Clinical Pharmacology,Anhui Medical University,Key Laboratory of Anti-inflammatory and Immune Medicine,Ministry of Education,Collaboratiwe Innovation Center of Anti-inflammatory and Immune Medicines,Hefei 230032)

机构地区：[1]安徽医科大学临床药理研究所,抗炎免疫药物教育部重点实验室,抗炎免疫药物安徽省协同创新中心,合肥230032

出　　处：《安徽医科大学学报》2020年第10期1550-1555,共6页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81974508、81673492)。

摘　　要：目的探讨芍药苷-6′-O-苯磺酸酯(CP-25)对胰岛素抵抗人主动脉平滑肌细胞(HASMC)的作用及部分机制。方法1μmol/L胰岛素诱导建立胰岛素抵抗HASMC模型;葡萄糖氧化酶法检测CP-25对胰岛素抵抗HASMC葡萄糖消耗量的影响;CCK-8法、Transwell、流式细胞术检测细胞的增殖、迁移和凋亡变化;Western blot法测定G蛋白偶联受体激酶2(GRK2)、胰岛素受体(INSR)、磷酸化胰岛素受体底物(p-IRS)、磷脂酰肌醇-3-激酶(PI3K)和葡萄糖转运体4(GLUT4)的表达;免疫共沉淀法测定GRK2与INSR、GRK2与p-IRS的相互作用。结果与胰岛素模型组相比,CP-25可增加HASMC的葡萄糖消耗,抑制其异常增殖和迁移、促进凋亡;1μmol/L胰岛素作用细胞后,CP-25下调胰岛素所致的GRK2的胞膜表达增高,上调IR-HASMC时INSR、p-IRS、PI3K的表达和GLUT4的胞膜表达;CP-25下调IR-HASMC时增高的GRK2与INSR、GRK2与p-IRS的共表达。结论CP-25可能通过抑制GRK2的膜转位和表达水平,促进INSR/IRS/PI3K/GLUT4信号通路的活化,改善HASMC的胰岛素抵抗。Objective To explore effect and mechanism of paeoniflorin-6′-O-benzenesulfonate(CP-25) on human aortic smooth muscle cell(HASMC) with insulin resistance(IR). Methods IR-HASMC was induced by 1 μmol/L insulin. We detected glucose consumption by glucose consumption assay kit. Cell proliferation, migration and apoptosis were detected by CCK-8, transwell and flow cytometry method respectively. The protein expression of GRK2, INSR, p-IRS, PI3 K and GLUT4 were determined by Western blot. The co-expressions of GRK2 and INSR, GRK2 and p-IRS were determined by co-immunoprecipitation. Results CP-25 increased the glucose consumption in IR-HASMC. CP-25 also inhibited abnormal proliferation and migration of cells, and promoted cell apoptosis. CP-25 down-regulated membrane expression of GRK2, up-regulated the expression of INSR, p-IRS, PI3 K and membrane expression of GLUT4. The co-expressions of GRK2 and INSR, GRK2 and p-IRS could be reduced by CP-25. Conclusion CP-25 can improve IR in HASMC, in which it inhibits the membrane translocation and expression of GRK2 and promotes activation of INSR/IRS/PI3 K/GLUT4 signaling pathway.

关 键 词：芍药苷-6′-O-苯磺酸酯 胰岛素抵抗 人主动脉平滑肌细胞 G蛋白偶联受体激酶2 胰岛素信号通路 

分 类 号：R965[医药卫生—药理学] R966[医药卫生—药学]