氯沙坦调节两肾一夹型高血压大鼠血管重塑及其与细胞外信号调节激酶1/2的关系  

Correlation between Vascular Remodeling Regulated by Losartan and Extracellular Signal-regulated Kinase-1/2 Activity in Two-kidney, One-cliped Hypertensive Rats

作　　者：徐立朋[1] 秦旭平[1] 廖端芳[1] 

机构地区：[1]南华大学药物药理研究所,湖南省衡阳市421001

出　　处：《中国动脉硬化杂志》2003年第1期17-21,共5页Chinese Journal of Arteriosclerosis

基　　金：国家 973项目 (G2 0 0 0 0 5 690 5 );国家自然科学基金( 30 1710 84)资助

摘　　要：为探讨特异性血管紧张素Ⅱ受体 1阻断剂氯沙坦调节高血压血管重塑与细胞外信号调节激酶的关系 ,本文采用两肾一夹型高血压大鼠为动物模型 ,术后第 2、4、6周测血压 ,6周后处死大鼠称心脏重量 ,取胸主动脉和肠系膜动脉作形态学观察和计算机图像分析 ,免疫印迹方法检测主动脉中磷酸化细胞外信号调节激酶及总细胞外信号调节激酶的表达。结果发现 ,与假手术对照组相比 ,模型组大鼠血压和心脏与体重之比分别增加 5 0 %和 48%(P均 <0 .0 1) ,主动脉和肠系膜动脉的内径与中膜厚度之比明显减少 (分别为 7.10± 0 .5 9比 9.2 4± 1.17,6.0 0± 0 .89比 8.96± 1.2 3 ) ,中膜厚度明显增加 (分别为 119.47± 10 .77μm比 91.5 5± 14.45 μm ,49.60± 1.0 4μm比 3 7.0 1± 4.85 μm ,P均 <0 .0 5 ) ,主动脉中磷酸化细胞外信号调节激酶的表达显著增强 ;氯沙坦治疗后 ,血压、心脏与体重之比分别下降到 13 2± 9mmHg、0 .3 2± 0 .0 3 (P均 <0 .0 5 ) ,主动脉和肠系膜动脉的内径与中膜厚度之比明显增加 ,中膜厚度明显减小 ,并下调主动脉中磷酸化细胞外信号调节激酶的表达。提示氯沙坦可明显改善两肾一夹型高血压大鼠的血管重塑 。Aim To investigate the effects and mechanisms of losartan, a specific blocker of angiotensin Ⅱ(Ang Ⅱ) receptor-1 (AT 1R) on vascular remodeling of two-kidney, one-cliped hypertensive rat. Methods The blood pressure (BP),heart weight (HW),and body weight (BW) were determined. The morphologic change of aortas and mesenteric resistance arteries was observed after staining with HE. Western blot was performed to valuate the ERK1/2 activity of aortas. Results The blood pressure,and HW/BW in hypertension group were significantly larger than that of control group (178±17 mm Hg vs 119±11 mm Hg, 0.40±0.07 vs 0.27±0.01 respectively, both P<0.01). Treatment with 20 mg/(kg·d) of losartan normalized BP(132±9 mmHg vs 178±17 mmHg,P<0.05) and HW/BW (0.32±0.03 vs 0.40±0.07,P<0.05). The lumen to media of mesenteric resistance arteries was decreased compared with control group (6.00±0.89 vs 8.96±1.23, P<0.01). Losartan normalized the lumen to media of hypertension group (8.87±1.25 vs 6.00±0.89,P<0.05). The p-ERK1/2 of aortas in hypertension group was overexpression compared with control group, and the overexpression of p-ERK1/2 was downregulated by treatment with losartan. Conclusion Losartan could regulate vascular remodeling in 2-kidney,1-cliped hypertensive rat by inhibiting the signaling pathway of ERK1/2.

关 键 词：细胞外信号调节激酶 氯沙坦 高血压 血管重塑 

分 类 号：R972.4[医药卫生—药品] R544.1[医药卫生—药学]