论文部分内容阅读
目的探讨罗格列酮(RSG)对高浓度葡萄糖孵育下的血管平滑肌细胞(VSMCs)炎症和凋亡的影响及其可能的分子机制。方法以不同浓度的葡萄糖和罗格列酮单独或联合孵育大鼠胸主动脉平滑肌细胞,ELISA方法检测培养基中单核细胞趋化蛋白-1(MCP-1)的水平;采用流式细胞术检测VSMCs细胞凋亡率及Bcl-xl、Bcl-2蛋白表达;Western印迹检测胞浆中VSMCsBcl-xl蛋白表达及NF-κBp65和IκBα的表达。结果高葡萄糖浓度(11.2、22.5mmol/L)培养可明显增加上清中MCP-1的浓度,促进VSMCs增殖,抑制其凋亡,上调Bcl-xl、Bcl-2蛋白表达,同时使NF-κBp65表达增加,IκBα表达下降;30及100μmol/LRSG以浓度依赖形式减少VSMCs对MCP-1的分泌,抑制高葡萄糖培养下(11.2、22.5mmol/L)VSMCsBcl-xl、Bcl-2表达,促进其凋亡;下调NF-κBp65表达,促进IκBα表达。RSG拮抗剂GW9662(10μmol/L)预处理可部分拮抗RSG的作用。结论 RSG可能通过对NF-κB通路的调控,减少炎症因子MCP-1分泌,下调Bcl-xl、Bcl-2表达,从而抑制高糖葡萄糖培养下的VSMCs炎症反应并促进其凋亡,从而在2型糖尿病大血管病变的防治中发挥重要作用。
Objective To investigate the effects of rosiglitazone (RSG) on the inflammation and apoptosis of vascular smooth muscle cells (VSMCs) incubated with high glucose and its possible molecular mechanisms. Methods Rat thoracic aortic smooth muscle cells were incubated with different concentrations of glucose and rosiglitazone alone or in combination. The level of monocyte chemoattractant protein-1 (MCP-1) in culture medium was detected by ELISA. Flow cytometry The apoptosis rate of VSMCs and the expression of Bcl-xl and Bcl-2 were detected by Western blotting. The expression of Bcl-xl and the expression of NF-κBp65 and IκBα in VSMCs were detected by Western blotting. Results Cultured with high glucose (11.2,22.5mmol / L) significantly increased the concentration of MCP-1 in the supernatant, promoted the proliferation and inhibited the apoptosis of VSMCs, up-regulated the expressions of Bcl-xl and Bcl-2 proteins, 30 and 100μmol / L RSG decreased the secretion of MCP-1 by VSMCs in a concentration-dependent manner, and inhibited the expression of Bcl-2, Bcl-2 and Bcl-2 in VSMCs under high glucose Decrease the expression of NF-κBp65 and promote the expression of IκBα. RSG antagonist GW9662 (10μmol / L) pretreatment can partially antagonize the role of RSG. Conclusion RSG may inhibit the secretion of Bcl-xl and Bcl-2 by inhibiting the secretion of inflammatory cytokines MCP-1 through regulating the NF-κB pathway, thus inhibiting the inflammatory response and promoting the apoptosis of VSMCs under high glucose. Type of diabetes prevention and treatment of macrovascular disease play an important role.