洛沙坦对心脏和动脉衰老保护作用的实验研究  

The experimental study of losartan's protective effect on cardiac and arterial aging

作　　者：白小涓[1] 李虹[1] 杨莹[1] 刘宇翔[1] 陈香美[2] 

机构地区：[1]中国医科大学附属第一医院循环内科,辽宁沈阳110001 [2]中国人民解放军总医院肾病中心

出　　处：《中国老年学杂志》2005年第2期171-173,共3页Chinese Journal of Gerontology

基　　金：国家重点基础研究发展规划项目资助(课题号:G2000057006)

摘　　要：目的观察老龄大鼠心肌纤维化程度、血管内皮依赖性舒张功能不全的变化及洛沙坦的干预作用,探讨血管紧张素II受体I(AT1R)拮抗剂(ARB)对心脏和动脉衰老的保护作用。方法Wistar大鼠30只,分为成年组、老龄组、洛沙坦组,生化法测心肌纤维化指标,免疫组化法测转化生长因子β1(TGFβ1)的表达。硝酸还原酶法测主动脉NO生成量,比色法测主动脉NOS活力。结果与成年组比较,老龄组心肌纤维化程度明显升高,TGFβ1表达上调,乙酰胆碱介导的内皮依赖性舒张反应受损(P<005),NO量及总NOS活力均显著降低(P<001)。与老龄组比较,洛沙坦组心肌纤维化程度明显降低(P<005),心肌TGFβ1表达减少,内皮依赖性舒张反应明显提高(P<001),NO量及总NOS活力均显著升高(P<005)。结论随着增龄,心肌纤维化程度增高,TGFβ1表达逐渐增加,血管内皮依赖性舒张功能减退。洛沙坦可抑制老龄大鼠心肌纤维化的形成,对增龄引起的血管内皮功能不良有改善作用。Objective By observing degree of myocardial fibrosis, changes of vascular endothelium dependent relaxation dysfunction of elderly rats and losartan's intervention effect, to explore the protective effect of angiotensin II receptor I antagonist on cardiac and arterial aging. Methods 30 Wistar rats were averagely divided into the young group (3~4 months old), the old group (18~20 months old) and losartan group (18~20 months old, given losartan 20 mg·kg^-1 ·d^-1 for 8 w), the indexes of myocardial fibrosis, TGF-β1 expression, NO production and NOS activity of aorta were determined by biochemical method, immunohistochemistry, nitrate reductase and colorimetry respectively. Results Comparing to those in the young group, degree of myocardial fibrosis and TGF-β1 expression increased, vascular endothelium dependent relaxation reaction induced by acetylcholine were damaged (P<0.05), NO production and total NOS activity also significantly decreased in the old group (P<0.01). Comparing to those in the old group, degree of myocardial fibrosis and TGF-β1 expression decreased, vascular endothelium dependent relaxation reaction significantly increased (P<0.01), NO production and total NOS activity all increased in the losartan group (P<0.05). Conclusions With aging, the degree of myocardial fibrosis and TGF-β1 expression increased, vascular endothelium dependent relaxation function gradually decreased. Losartan could not only inhibit the degree of myocardial fibrosis in elderly rats, but also improve vascular endothelium dysfunction induced by aging.

关 键 词：衰老 心肌纤维化 动脉 洛沙坦 血管紧张素 

分 类 号：R339.38[医药卫生—人体生理学]