福辛普利对自发性高血压大鼠脑超微结构及Klotho基因表达的影响

目的 观察药物干预后高血压脑损害的超微结构及其脑组织中Klotho基因和微炎症因子--血管细胞粘附分子1和细胞间粘附分子1的表达状况.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福辛普利干预组(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,通过RT-PCR检测、免疫组织化学技术和western印迹检测Klotho基因和微炎症因子血管细胞粘附分子1和细胞间粘附分子1的表达状况.结果 高血压损害脑神经元的结构、主要表现为细胞固缩、染色质边集、典型凋亡小体形成,但经过福辛普利干预后,其神经元损害有所减轻.RT-PCR结果显示福辛普利干预能够上调Klotho基因mRNA表达(P<0.05)、下调微炎症因子血管细胞粘附分子1和细胞间粘附分子1mRNA的表达(P<0.01);免疫组织化学技术和Western-blot检测证实福辛普利干预能够增加Klotho蛋白的表达,同时减血管细胞粘附分子1和细胞间粘附分子1蛋白的表达.结论 福辛普利能够上调Klotho的表达,改善高血压脑超微结构的改变.

Changes of the Ultrastructure in the Brain Tissue and Effect of Expression of Klotho Gene of the Spontaneously Hypertensive Rat Interference with Fosinopril

Aim To observe the changes of the ultrastructure and expression of Klotho,intercellular adhesion molecular-1(ICAM-1)and vascular cellular adhesion molecular-1(VCAM-1)genes in the brain tissue of the spontaneously hypertensive rat model treated by medicines. Methods 10 male spontaneously hypertensive rats of 22 weeks age were selected and randomly divided to hypertension and Fosinopril interventive groups,while 5 Wistar-kyoto rats were setted as normal contrast group. The brain ultrastructure of all groups were observed by electron microscope. The expression status of micro-inflammatory factor(ICAM-1 and VCAM-1)and Klotho gene were detected with RT-PCR,immunohistochemistry and western blotting. Results Hypertension might affect the structures of brain neuron,such as nucleus aggregation,nucleus condensation,nucleus fragmentation and apoptotic body formation. But fosinopril treatments could reduce the damage of brain neuron. By RT-PCR Fosinopril treatments could up-regulate the mRNA expression of Klotho gene(P><0.05) and down-regulate the mRNA expression of ICAM-1 and VCAM-1gene in the brain tissue of the SHR group(P><0.01). At the same time,the results of immunohistochemistry and western-blot verified that fosinopril increased the protein expression of Klotho and depressed the protein expression of ICAM-1 and VCAM-1. These results suggested that fosinopril could protect the neuron function by regulating the expression of Klotho gene and ICAM-1 and VCAM-1. Conclusion Fosinopril could resume the ultrastructure in the brain tissue of the spontaneously hypertensive rat.