磷酸化细胞外信号调节激酶和P^(21ras)在高血压血管平滑肌细胞中表达增强(英文)  

P^(21ras) and phosphorylated extracellular signal-regulated protein kinase are highly expressed in vascular smooth muscle cells of hypertensive rats

作　　者：景丽[1] 张建忠[2] 王一理[1] 郭风英[2] 

机构地区：[1]西安交通大学生命科学与技术学院免疫病理研究室,陕西西安710061 [2]宁夏医学院病理学教研室,宁夏银川750004

出　　处：《南方医科大学学报》2006年第7期895-900,共6页Journal of Southern Medical University

基　　金：Natural Science Foundation of Ningxia (nz0651).

摘　　要：目的探讨高血压血管平滑肌细胞增生和ERK激活的机制。方法采用免疫组织化学和Westernblotting技术,对比观察肾血管性高血压和自发性高血压大鼠肾细小动脉平滑肌细胞中磷酸化细胞外信号调节激酶1/2(ERK1/2)和P21ras表达。结果实验期间,Wistar肾血管性高血压组动脉血压从(104±18)mmHg升高到实验结束时的(198±33)mmHg,自发性高血压大鼠16周龄时的血压为(163±23)mmHg。肾血管性高血压组肾小球发生了明显的纤维化(P<0.05),自发性高血压大鼠肾小球纤维化等与对照组无显著性差异。肾血管性高血压组入球动脉、小叶间动脉、叶间动脉和弓形动脉血管平滑肌细胞中磷酸化ERK1/2染色阳性率分别为7.09%、14.57%、29.44%和13.63%,均明显高于对照组(P<0.01)。自发性高血压大鼠入球动脉、小叶间动脉、叶间动脉和弓形动脉血管平滑肌细胞中磷酸化ERK1/2染色阳性率分别为16.09%、24.17%、32.44%和18.61%,均明显高于对照组(P<0.01);肾血管性高血压组和16周龄自发性高血压大鼠入球动脉、小叶间动脉和弓形动脉平滑肌细胞中P21ras的阳性率明显高于对照组(P<0.01);Westernbloting检测可见高血压组和16周龄自发性高血压大鼠肾组织磷酸化ERK1/2和P21ras蛋白含量明显高于对照组(P<0.01)。结论在大鼠两肾一夹型高血压和自发性高血压时,P21ras基因表达增加使部分血管平滑肌细胞丝裂原激活蛋白激酶系统激活,导致部分小动脉血管平滑肌细胞增生。Objective To investigate the molecular mechanisms of vascular smooth muscle cell （VSMC） hyperplasia and extracellular signal-regulated protein kinase 1/2 （ERK 1/2） phosphorylation of VSMCs under the condition of hypertension. Methods Wistar rat models of two kidney-one clip hypertension （2K1C） were established and their right kidneys were harvested 4 weeks after the operation. Immunohistochemistry and Western blotting were performed to detect phospho-ERK1/2 and P^21ras protein expression in the VSMCs of the renal arterioles, and the results were compared with those from 16-week-old spontaneous hypertension rats （SHR16） and control rats. Results The blood pressure of2K1C Wistar rats was significantly increased from 104±18 mmHg to 198±33 mmHg at the end of the experiment, and the blood pressure of SHR16 reached 163± 23 mmHg, significantly higher than that of the control rats （P〈0.01）. Compared with the control group, 2K1C rats showed obvious glomerular fibrosis （P〈0.05） with hyaline degeneration of the afferent arterioles. In contrast, neither glomerular fibrosis nor hyaline degeneration of arterioles, nor protein cast was observed in SHR16. In 2K1C rats and SHR16, the positivity rates of phospho-ERK1/2 and P^21ras staining in the VSMCs of the afferent arterioles and the interlobular, interlobar and arcuate arteries was significantly higher than those of the controls （P〈0.01）, and the expression ofphospho-ERK1/2 and P^21ras protein in the kidney was also significantly higher as revealed by Western blotting （P〈0.01）. Conclusion High expression of ERK1/2 and P^21ras in the renal arteriole VSMCs of 2K1C hypertensive rats and SHR may play an important role in VSMC hypertrophy and proliferation in hypertension.

关 键 词：高血压 血管平滑肌细胞 细胞外信号调节激酶 P^21RAS 大鼠 

分 类 号：R544.1[医药卫生—心血管疾病]