地黄饮子改善自发性高血压大鼠进程中血管内皮功能的研究

Effect of Dihuang Yinzi on Hypertension Development in Spontaneously Hypertensive Rats:Role of Improving Endothelial Function

目的:探讨自发性高血压大鼠(SHR)高血压发展进程中,地黄饮子对其血管内皮功能的修复情况及作用机制研究。方法:54只雄性SHR随机分为3组:模型组、地黄饮子组和卡托普利组,7～24周龄ig地黄饮子(生药15.9 g.kg-1.d-1)和卡托普利(3.375 g.kg-1.d-1),停药观察至32周龄。18,24,32周龄时分别颈动脉插管测定大鼠血压值,血管等长张力实验检测离体肠系膜上动脉乙酰胆碱(Ach)依赖性舒张功能;Griess法检测血清NO 2-水平;实时荧光定量PCR(Real-time PCR)检测动脉组织白介素-1(IL-1),白介素-6(IL-6),肿瘤坏死因子-α(TNF-α)和iNOS mRNA)的表达。结果:地黄饮子降低SHR 18周龄血压,增加18,24周龄肠系膜上动脉Ach依赖性舒张功能和血清NO 2-含量,显著降低动脉组织IL-1,IL-6,TNF-α和iNOSmRNA表达;卡托普利降压作用优于地黄饮子,停药后作用消失,无改善肠系膜上动脉Ach依赖性舒张功能作用,增加血清24周龄NO 2-水平和动脉组织IL-1,IL-6 mRNA表达的同时降低TNF-α和iNOS表达。结论:地黄饮子能显著改善SHR肠系膜上动脉内皮功能,表现为较好的抗高血压作用。该作用可能与其抑制IL-1,IL-6,TNF-α和iNOS表达,改善血管微环境的炎症反应状态有关。

Objective：To investigate the action mechanism of Dihuang Yinzi on hypertension progress of spontaneously hypertensive rats（SHR）,and understand the role of endothelial function recovery by Dihuang Yinzi.Method：Fifty-four male SHR were divided into three groups：the control;Dihuang Yinzi treatment;and captoril treatment.Dihuang Yinzi（crude drug 15.9 g.kg-1.d-1） and captoril（3.375 g.kg-1.d-1） were treated from wk 7 to wk 24（wk = week） through gavage.The drug effect was observed at wk 18 and wk 24 during the treatments and 8 wk（wk32） after treatment.Experiments including the blood pressure by arterial carotis cannula;the concentration of NO 2-by Griess;the Ach-dependent relaxation of mesenteric rings by isometric tension change;and the mRNA expressions of IL-1,IL-6,TNF-α and iNOS of aorta tissue by real time PCR.Result：Dihuang Yinzisignificantly reduced blood pressure at wk18,and increased Ach-dependent relaxation of mesenteric rings and the NO 2-concentration in serum at wk18 and wk24.The mRNA expression of IL-1,IL-6,TNF-α and iNOS was markedly inhibited by the herb formula.Although captopril showed stronger anti-hypertensive effect,which could not extended after drug withdraw.In addition,the beta blocker did not enhance Ach-dependent vasodilation.NO 2-levels in serum and IL-1,IL-6 expression of aorta tissue were increased by captopril,while iNOS and TNF-α were inhibited at wk 24.Conclusion：Dihuang Yinzi showed anti-hypertensive effect with enhanced endothelium-dependent vasodilation in mesenteric artery and increased NO 2-concentration in serum.Furthermore,the herb formula also exerted anti-inflammatory effect by decreasing IL-1,IL-6,TNF-α and iNOS expression.