目的 研究白藜芦醇对环孢菌素A（cyclosporine A，CsA）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CsA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 CsA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-HT_1B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-HT_1B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-HT_1B 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-HT_1B 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.

R285.5

国家自然科学基金资助项目（81800401）；陕西省科技厅一般项目——社会发展领域（2022SF-207，2022SF-435）；大学生创新创业训练计划项目（S202010716021，S202010716024）；陕西中医药大学学科创新团队（2019-YL13）