缬沙坦对自发性高血压大鼠脑超微结构和Klotho基因表达的影响

Effect of valsartan on ultrastructure in the brain tissue and expression of Klotho gene in spontaneously hypertensive rats

目的:探讨缬沙坦对自发性高血压模型鼠脑超微结构及其脑组织中Klotho基因和微炎症因子(ICAM-1和VCAM-1)表达的影响。方法:选取22周龄雄性自发性高血压模型鼠10只,随机分为高血压组与缬沙坦组(5只/组),Wistar-kyoto大鼠(WKY)5只作为正常对照组。通过电镜观察各组大鼠脑的超微结构,RT-PCR、免疫组织化学技术和Western印迹检测Klotho基因和微炎症因子(ICAM-1和VCAM-1)的表达。结果:高血压组大鼠脑神经元细胞的超微结构主要表现为细胞固缩、染色质边集、典型凋亡小体形成,但经过缬沙坦干预后,其神经元损害有所减轻。RT-PCR结果显示缬沙坦干预能够上调KlothomRNA表达水平、下调微炎症因子ICAM-1和VCAM-1mRNA的表达;免疫组织化学技术和Western印迹检测证实缬沙坦干预能够增加Klotho蛋白、减少ICAM-1和VCAM-1蛋白的表达。结论:缬沙坦能够上调Klotho的表达,改善高血压脑超微结构的改变。

Objective To observe the effect of valsartan on brian ultrastructure,Klotho gene and micro-inflammatory factor [intercellular adhesion molecule-1（ICAM-1）and vascular cell adhesion molecule-l（VCAM-1）] expression in spontaneously hypertensive rat models.Methods Ten male spontaneously hypertensive rats of 22 weeks age were selected and randomly divided into a hypertension group and a valsartan intervention group,while another 5 Wistar-kyoto rats were set as a normal contrast group.The brain ultrastructure of the 2 groups was observed by electron microscope.The expression of micro-inflammatory factor（ICAM-1 and VCAM-1）and Klotho gene was detected with RT-PCR,immunohistochemistry,and Western blot,respectively.Results The cerebral neuron damage of spontaneously hypertensive rats whose ultrastructure showed cell-pyknosis,chromatin margination and typical apoptotic body formation were alleviated after the intervention of valsartan.RT-PCR showed that the gene expression of Klotho increased while ICAM-1 and VCAM-1 decreased after valsartan intervention.Immunohistochemistry and Western blot also showed that the protein expression of Klotho increased,while ICAM-1 and VCAM-1 decreased after valsartan intervention.ConclusionValsartan can improve the brain ultrastructure of spontaneously hypertensive rats by increasing the expression of Klotho.