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OA北大核心CSTPCD

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(HbAlc),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(IKBα)and nuclear factor KBp65(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-KBp65 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 indicators were improved(P＜0.05,P＜0.01).In ZJTF-H group,part of the carotid endothelium was exfoliated and the shape of the nucleus was more regular.The protein expression and mRNA levels of GPR43 and IκBα significantly increased(P＜0.05,P＜0.01).The protein expression and mRNA levels of β-arrestin-2 and NF-KBp65 significantly decreased(P＜0.01).Conclusion Zuogui Jiangtang Tongmai Formula can improve vascular endothelial dysfunction in T2DM rats,and its mechanism may be related to the regulation of GPR43/β-arrestin-2/IκBα/NF-κB signaling pathway.