Rho激酶抑制剂对压力超负荷大鼠血管紧张素(1-7)的影响  

Impact of Fasudil on cardiac and plasma Angiotensin(1-7) in pressure-overload rats

作　　者：蔡辉[1] 张培勇[1] 董晓蕾[1] 赵凌杰[1] 赵智明[1] 

机构地区：[1]南京军区南京总医院中西医结合科,南京医学博士210002

出　　处：《医学研究生学报》2013年第11期1142-1146,共5页Journal of Medical Postgraduates

基　　金：南京军区南京总医院科研基金(2010Q027)

摘　　要：目的抑制Rho激酶的活性表现出抗心肌纤维化的能力,然而其机制尚不甚清楚。实验观察Rho激酶抑制剂法舒地尔对压力超负荷大鼠心肌和血浆AngⅡ及其水解七肽血管紧张素(1-7)[Ang(1-7)]的影响。方法采用腹主动脉缩窄术制备SD大鼠压力超负荷模型,术后4周随机分为4组:假手术组、模型组、法舒地尔高剂量组[FH,30 mg/(kg·d)]和法舒地尔低剂量组[FL,10 mg/(kg·d)]组。术后8周计算大鼠左心室质量指数(left ventricular weight index,LVWI),观察心肌组织HE染色和Masson胶原染色,碱水解法测定羟脯氨酸(hydroxyproline,HYP)含量,ELISA检测心肌和血浆AngⅡ和Ang(1-7)的浓度。结果与假手术组相比,模型组大鼠LVWI及HYP含量显著升高(P<0.01),间质大量胶原蛋白沉积,心肌和血浆AngⅡ升高,心肌Ang(1-7)降低(P<0.01),而血浆Ang(1-7)改变无统计学意义;与模型组相比,FH组和FL组大鼠LVMI及HYP含量均降低(P<0.05),间质胶原蛋白沉积程度减轻,FH组心肌和血浆AngⅡ浓度降至正常水平(P<0.01),心肌和血浆Ang(1-7)升高均有统计学意义(P<0.01)。FL组心肌和血浆AngⅡ降低(P<0.05),心肌和血浆Ang(1-7)浓度升高(P<0.01)。结论法舒地尔可抑制压力超负荷诱导的大鼠心肌纤维化的作用可能与AngⅡ水平降低及Ang(1-7)水平升高有关。Objective Rho-kinase inhibition displays an activity against cardiac fibrosis, though its mechanism has not been fully elucidated. The present study was to investigate the impact of fasudil, a Rho kinase inhibitor, on cardiac and plasma Angiotensin Ⅱ （Ang Ⅱ ） and Angiotensin（1-7） [ Ang（ 1-7 ） ] in pressure-overload rats. Methods Pressure-overload models were made in SD rats by abdominal aorta constriction, and 4 weeks after surgery the animals were randomly divided into 4 groups ： sham, model, high- dose fasudil （HF, 30 mg per kg per d） and low-dose fasudil （LF, 10 mg per kg per d）. At 8 weeks after surgery, the left ventricle/ weight index （LVWI） was calculated, the content of cardiac hydroxyproline （HYP） measured using alkaline hydrolysis, myocardial histopathology and interstitial fibrosis observed by HE and masson staining, and the concentrations of cardiac and plasma Ang Ⅱ and Ang（1-7） detected by ELISA. Results Compared with the sham group, the model group showed significantly elevated contents of LVWI and HYP （P 〈 0. O1 ）, much more collagen deposited in the myocardial interstitium, increased concentration of cardiac and plasma Ang Ⅱ, and decreased level of cardiac Ang（ 1-7 ） （ P 〈 O. 01 ）, but a similar level of plasma Ang（ 1-7 ）. In comparison with the model group, the HF and LF groups exhibited reduced contents of LVMI and HYP and decreased deposition of interstitial collagen. Theconcentrations of cardiac and plasma Ang Ⅱwere reduced to normal, while cardiac and plasma Ang（ 1-7 ） increased significantly in the HF group （P 〈0.01 ）. The concentrations of cardiac and plasma Ang Ⅱ were significantly reduced （ P 〈 O. 05 ）, while Ang （ 1-7 ） remarkably increased in the LF group （P 〈 0.01 ）. Conclusion Fasudil can attenuates pressure-overload mediated cardiac fibrosis, which may beassociated with the reduced level of Ang Ⅱ and increased level of Ang（1-7）.

关 键 词：法舒地尔 心室重构 心肌纤维化 肾素-血管紧张素系统 

分 类 号：R972[医药卫生—药品]