基于SIRT1-ERK1/2通路研究白藜芦醇对环孢菌素A诱导高血压的作用及机制

Effect and mechanism of resveratrol on cyclosporin A-induced hypertension based on SIRT1-ERK1/2 pathway

目的研究白藜芦醇对环孢菌素A(cyclosporine A,Cs A)诱导高血压的作用及其机制。方法采用离体血管培养技术和微血管张力描记技术研究Cs A对5-羟色胺(5-hydroxytryptamine,5-HT)介导的平滑肌收缩量效曲线变化。大鼠sc Cs A诱导血压升高,给予白藜芦醇进行干预,研究白藜芦醇对血压的影响;采用微血管张力描记观察5-HT引起的动脉收缩量效曲线的变化;采用Western blotting检测5-HT1B受体、沉默信息调节因子1(sirtuin 1,SIRT1)、细胞外信号调节激酶1/2(extracellular regulated kinase 1/2,ERK1/2)蛋白表达。结果离体血管培养结果表明,白藜芦醇通过激活SIRT1-ERK1/2通路抑制CsA诱导的收缩。动物实验表明白藜芦醇可以显著降低CsA引起的血压升高(P<0.05、0.01);抑制5-HT引起的收缩反应(P<0.05、0.01);降低5-HT1B受体和p-ERK1/2蛋白表达(P<0.05、0.01),增加SIRT1蛋白表达(P<0.01)。结论白藜芦醇通过SIRT1-ERK1/2信号通路下调5-HT受体,从而抑制CsA诱导的高血压。

Objective To study the effect and mechanism of resveratrol on cyclosporine A(CsA) induced hypertension.Methods In vitro organ culture and myograph were used to study CsA induced vasoconstrictions mediated by 5-hydroxytryptamine(5-HT) receptor.Rats were sc CsA to induce blood pressure increased,and resveratrol was given for intervention to study the effect of resveratrol on blood pressure;Microvascular tonometry was used to observe the changes in dose-response curve of arterial contraction caused by 5-HT;Western blotting was used to detect 5-HT1B receptor,sirtuin 1(SIRT1) and extracellular regulated kinase 1/2(ERK1/2) protein expressions.Results The results of isolated blood vessel culture showed that resveratrol inhibited CsA-induced contraction by activating SIRT1-ERK1/2 pathway.Animal experiments showed that resveratrol could significantly reduce the increase in blood pressure caused by CsA(P < 0.05,0.01);Inhibited the contractile response caused by 5-HT(P < 0.05,0.01);Decreased the expressions of 5-HT1B receptor and p-ERK1/2 protein(P < 0.05,0.01),and increased the protein expression of SIRT1(P < 0.01).Conclusion Resveratrol can inhibit CsA-induced hypertension by down-regulating 5-HT receptor through SIRT1-ERK1/2 signaling pathway.