氯沙坦或卡托普利对自发性高血压大鼠心脏纤维化的干预研究

Effects of Losartan and Captopril on Myocardial Fibrosis in Spontaneously Hypertensive Rats

目的 探讨在不同水平阻断肾素 -血管紧张素系统 (RAS)对高血压心肌纤维化的影响。方法 2 9只自发性高血压大鼠 (SHR)随机分成 (1)SHR对照组 (n =15 ) ;(2 )氯沙坦组 (n =7,30mg·kg-1·d-1) ;(3)卡托普利组 (n =7,10 0mg·kg-1·d-1) ;(4)WKY(n =12 )为非高血压组。治疗组每日灌胃给药 ,对照组蒸馏水灌胃 15周后 ,获取标本。结果 1.SHR心肌血管紧张素Ⅱ (AngⅡ )和醛固酮 (Ald)浓度、羟脯氨酸和Ⅰ /Ⅲ型胶原比值较同龄WKY大鼠明显增高 (P <0 0 1) ,而心肌胶原单体 /二聚体 (α/ β)比值和基质金属蛋白酶 - 1(MMPs- 1)活力降低 (P <0 0 1) ,且随病程而进一步升高或降低。 2 .经氯沙坦或卡托普利干预后 ,心肌AngⅡ、Ald浓度、心肌羟脯氨酸和Ⅰ、Ⅲ型胶原比值有不同程度的降低 (P <0 0 1) ,而心肌胶原单体 /二聚体 (α/ β)比值和MMPs- 1活性升高 (P <0 0 1) ,逆转了心肌纤维化。3.氯沙坦在改善胶原表型、胶原可溶性及提高MMPs- 1活性优于卡托普利。结论 不同水平阻断肾素血管紧张素系统对纤维化逆转不仅减少胶原含量 。

Objective To investigate the change of myocardial fibrosis in spontaneously hypertensive rats(SHR) by inhibition the renin angiotensin system in different level. Methods Twenty nine males SHR (15 weeks old) were divided into four groups: SHR control group(SHR15W, n =7; SHR30W, n =8); Losarton group(SHRLos, n =7); Captopril group (SHRCap, n =7); Wistar kyoto(WKY) control group(WKY15W, n =6;WKY30W, n =6). The control group were treated with tap water. Losartan or captopril was dissolved in tap water and given to SHRLos or SHRCap at the dose of 30 mg·kg -1 ·d -1 or 100 mg·kg -1 ·d -1 . The rats were sacrificed after 15 weeks and free wall and septum of left ventricular were examined. Results (1) Angiotension Ⅱ, aldosterone, hydroxyproline, ratio of of typeⅠ/Ⅲ collagens in myocardium of SHR were increaed significantly than age matched WKY( P <0 01) Collagen α/β ratio and metalloproteinase 1 activity were decreased. (2) After treatment with losartan or captopril, angiotension Ⅱ, aldosterone, ratio Ⅰ/Ⅲ collagens in myocardium of SHR were decreased substantially. The ratio of collagen α/β and metalloproteinase 1 activity were increased in treatment groups. Losartan or captopril reverse myocardial fibrosis. (3) Losartan is more effective than captopril in the improve collagen phenotypes, decreases in cross linked and promote metalloproteinase 1 activity ( P <0 01). Conclusion Losartan and captopril reverse myocardial fibrosis not only by decreasing collagen content and cross linked but also improvement collagen of phenotypes and promoted metalloproteinase 1 activity.