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

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Klotho mRNA表达水平、下调微炎症因子ICAM-1和VCAM-1 mRNA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。

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

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.