基于GPR43/β-arrestin-2/IκBα/NF-κB通路探讨左归降糖通脉方对糖尿病大鼠血管内皮炎性保护的影响  

Effect of Zuogui Jiangtang Tongmai Formula on Vascular Endothelial Inflammation Protection in Diabetic Rats Based on GPR43/β-arrestin-2/IκBα/NF-κB Pathway

作　　者：彭岚玉 李定祥 姚敬心 蔡昱哲 邓奕辉 PENG Lan-yu;LI Ding-xiang;YAO Jing-xin;CAI Yu-zhe;DENG Yi-hui(School of Integrated Chinese and Western Medicine,Hunan University of Chinese Medicine,Changsha(410208);School of Traditional Chinese Medicine,Hunan UniversityofChineseMedicine,Changsha(410208))

机构地区：[1]湖南中医药大学中西医结合学院,长沙410208 [2]湖南中医药大学中医学院,长沙410208

出　　处：《中国中西医结合杂志》2024年第5期558-566,共9页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：湖南省教育厅科学研究项目(No.20 A365,No.21 A0228);湖南省中医药科研计划项目(No.E2022010);湖南中医药大学中西医结合一流学科开放基金(No.2020 ZXYJH31)。

摘　　要：目的 研究左归降糖通脉方对2型糖尿病(T2DM)大鼠血管内皮功能障碍的影响与作用机制。方法 高脂饲料喂养联合链脲佐菌素腹腔注射的方法制备模型。将SD大鼠随机分为空白组、模型组、左归降糖通脉方低剂量(12 g/kg,ZJTF-L)组、左归降糖通脉方高剂量(24 g/kg,ZJTF-H)组、二甲双胍+阿托伐他汀(150 mg/kg+10 mg/kg、西药联用)组、短链脂肪酸(500 mg/kg,SCFAs)组,每组10只。干预结束后,采用透射电镜观察大鼠颈动脉超微结构变化;ELISA检测血清胰岛素(FINS)、糖化血红蛋白(HbAlc)、细胞间黏附分子1(ICAM-1)、血管内皮细胞黏附分子1(VCAM-1)、内皮素1(ET-1)、白细胞介素-1 β(IL-1 β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)的水平;生化分析法检测血清一氧化氮(NO)的含量;分别采用Western Blot、q PCR检测G蛋白偶联受体43(GPR43)、β-抑制蛋白2(β-arrestin-2)、核因子κB抑制因子α(IκBα)、核因子κB p65(NF-κBp65)的蛋白表达与mRNA水平。结果 与空白组比较,模型组体重下降,血糖显著升高(P<0.01);HbA1 c、FINS、IL-1 β、IL-6、TNF-α、ICAM-1、VCAM-1及ET-1水平明显升高,NO明显降低(P<0.01);内皮细胞肿胀,胞核皱缩,细胞形状不清晰;颈动脉GPR43、IκBα蛋白表达与mRNA水平显著降低(P<0.05,P<0.01),β-arrestin-2、NF-κBp65蛋白表达与mRNA水平显著升高(P<0.01)。与模型组比较,药物干预各组体重升高、血糖下降(P<0.01);炎症因子、血管内皮功能各项指标均有所好转(P<0.05,P<0.01)。ZJTF-H组颈动脉部分内皮脱落,胞核形状较规则;GPR43、IκBα蛋白表达与mRNA水平明显升高(P<0.05,P<0.01);β-arrestin-2、NF-κBp65蛋白表达与mRNA水平明显下降(P<0.01)。结论 左归降糖通脉方可改善T2DM大鼠血管内皮功能障碍,其机制可能与调节GPR43/β-arrestin-2/IκBα/NF-κB信号通路有关。Objective To study the effect and mechanism of Zuogui Jiangtang Tongmai Formula on vascular endothelial dysfunction in type 2 diabetes mellitus(T2DM) rats. Methods High fat feed combined with streptozotocin intraperitoneal injection was used to prepare the model. SD rats were randomly divided into blank group,model group,Zuogui Jiangtang Tongmai Formula low dose(12 g/kg, ZJTF-L) group,Zuogui Jiangtang Tongmai Formula high dose(24 g/kg, ZJTF-H) group,metformin + atorvastatin(150 mg/kg+10 mg/kg,Western medicine) group, short-chain fatty acid(500 mg/kg,SCFAs) group,10 in each group. After the intervention,the ultrastructural changes of carotid artery in rats were observed by transmission electron microscopy. Serum insulin(FINS) and glycosylated hemoglobin(Hb Alc),intercellular adhesion molecule 1(ICAM-1),vascular endothelial cell adhesion molecule 1(VCAM-1),endothelin 1(ET-1),interleukin-1 β(IL-1 β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α) were detected by ELISA. The content of nitric oxide(NO) was detected by biochemical analysis. The protein expression and mRNA levels of G protein-coupled receptor 43(GPR43),β-suppressor protein 2(β-arrestin-2),nuclear factor κB suppressor α(IκBα) and nuclear factor κBp65(NF-κBp65) were detected by Western Blot and qPCR. Results Compared with blank group,body weight decreased and blood glucose increased significantly in model group(P<0.01). The levels of HbA1c, FINS, IL-1 β, IL-6, TNF-α,ICAM-1, VCAM-1 and ET-1 were significantly increased,while the levels of NO were significantly decreased(P<0.01).Endothelial cell swelling,nucleus shrinkage and cell shape was not clear. The protein expression and mRNA levels of GPR43 and IκBα in carotid artery significantly decreased(P<0.05,P<0.01),and the protein expression and mRNA levels of β-arrestin-2 and NF-κBp65 significantly increased(P<0.01).Compared with model group,body mass decreased and blood glucose increased in drug intervention groups(P<0.01). Inflammatory factors and vascular endothelial function indicat

关 键 词：左归降糖通脉方 2型糖尿病 G蛋白偶联受体43 β-抑制蛋白2 核因子κB抑制因子α 核因子ΚB 中药复方 

分 类 号：R285.5[医药卫生—中药学]