摘要
目的探讨法舒地尔对压力超负荷大鼠心肌血管紧张素转换酶2(ACE2)和血管紧张素(1-7)[Ang(1-7)]的影响。方法 50只SD大鼠制备压力超负荷模型,术后4周末,将存活36只大鼠随机分为假手术组8只、模型组10只、法舒地尔高剂量组(高剂量组)9只和法舒地尔低剂量组(低剂量组)组9只。术后8周末,计算各组左心室质量指数(LVMI);观察心肌组织HE和Masson胶原染色;碱水解法测定心肌羟脯氨酸(HYP)含量;免疫组织化学分析ACE和ACE2水平;RT-PCR和ELISA法分别检测ACE2mRNA表达、AngⅡ和Ang(1-7)浓度。结果与假手术组比较,模型组心肌间质大量胶原蛋白沉积,LVMI、HYP、ACE和AngⅡ明显升高,ACE2、ACE2mRNA及Ang(1-7)明显降低(P<0.01);与模型组比较,高剂量组和低剂量组LVMI、HYP明显降低,间质胶原蛋白沉积明显减轻,ACE和AngⅡ明显降低(P<0.05),ACE2、ACE2mRNA和Ang(1-7)明显升高(P<0.01)。结论法舒地尔抑制压力超负荷诱导的心肌纤维化的作用可能与局部ACE-AngⅡ及ACE2-Ang(1-7)的改善有关。
Objective To study the effect of fasudil on angiotensin converting enzyme 2 (ACE2) and angiotensin (1-7) in rat myocardium. Methods An overload pressure model of SD rats was established by constricting abdominal aorta. Four weeks after operation, the rats were divided into sham operation group (n=8),model group (n=10), high fasudil dose group (n=9), and low fa- sudildose group (n=9). At the 8 weekend after operation,left ventricle mass index (LVMI) was calculated,myocardial hydroxyproline (HYP) level in myocardial tissues stained with HE and Masson collagen was measured by alkaline hydrolysis. ACE and ACE2 protein levels were meas- ured by immunohistoehemieal analysis. Expression of ACE2 mRNA was detected by RT-PCR and Western blot,respectively. Angiotensin Ⅱ and angiotensin (1-7)levels were measured by ELISA. Results The LVMI and the levels of HYP,collagen deposition in myocardial interstitium,ACE, angiotensin Ⅱ were significantly higher whereas the levels of ACE2,ACE2 mRNA and angiotensin (1-7) were significantly lower in model group than in sham operation group (P〈0. 01). The LVMI and the levels of HYP, collagen deposition in myocardial interstitium,ACE and angiotensin Ⅱ were significantly lower whereas the levels of ACE2 protein, ACE2 mRNA and angiotensin (1-7) were significantly higher in high and low fasudil dose groups than in model group (P〈 0. 05,P〈0. 01). Conclusion Fasudil inhibits overload pressure-induced myocardial fibrosis by improving ACE2 and angiotensin (1-7).
出处
《中华老年心脑血管病杂志》
CAS
北大核心
2013年第5期521-525,共5页
Chinese Journal of Geriatric Heart,Brain and Vessel Diseases
基金
南京军区南京总医院科研基金(2010Q027)