阿托伐他汀对自发性高血压大鼠颈总动脉血管紧张素转换酶2表达的影响

目的观察阿托伐他汀对自发性高血压大鼠(SHR)颈总动脉血管紧张素转换酶2(ACE2)表达的影响及其改善血管重构的可能作用机制。方法24只13周龄雄性SHR随机分为3组(每组8只):SHR组(0.5%阿拉伯胶浆15 mg·kg~(-1)·d~(-1))、阿托伐他汀组(30 mg·kg~(-1)·d~(-1))、缬沙坦组(20 mg·kg~(-1)·d~(-1));8只同周龄雄性WKY大鼠作为正常血压对照组(WKY组)(0.5%阿拉伯胶浆15 mg·kg~(-1)·d~(-1))。连续灌胃给药4周后处死。放免分析法测定血浆和颈总动脉血管紧张素Ⅱ(AngⅡ)浓度;病理图像分析系统测定颈总动脉内膜增生程度和中膜增生面积。免疫组化法检测颈总动脉ACE 2蛋白表达;RT-PCR法检测颈总动脉ACE 2 mRNA的表达。结果(1)与SHR组比较,阿托伐他汀组和缬沙坦组内膜增生程度显著降低(P<0.01),且缬沙坦组优于阿托伐他汀组(P<0.05),但2组中膜增生面积差异无统计学意义(P>0.05)。(2)与SHR组比较,阿托伐他汀组、缬沙坦组颈总动脉AngⅡ浓度降低(P<0.01),血浆AngⅡ浓度、ACE 2 mRNA和蛋白表达显著升高(P<0.01),且缬沙坦组优于阿托伐他汀组(P<0.05,P<0.01)。结论阿托伐他汀可显著抑制血管内膜增生,与其降低颈总动脉AngⅡ浓度、升高ACE 2 mRNA和蛋白表达有关。

Therapeutic effect of atorvastatin on the expression of angiotensin converting enzyme 2 in carotid common artery of spontaneously hypertensive rats

Objective To observe the effect of atorvastatin on the expression of ACE 2 on intimal hyperplasia of carotid common artery in SHR,and to explore the possible mechanism of atorvastain on vascular remodeling.Met hods Thirteen weeks old male SHR（n=24） were randomized divided into three groups（n=8,each）,SHR control group（0.5%acacia mucilage,15 mg·kg·d~（-1））,atorvastatin treatment group（30 mg·kg^-1·d^-1） and valsartan treatment group（20mg·kg^-1·d^-1）.Eight age matched male Wistar-Kyoto rats were selected as the normal control（WKY group,0.5%acacia mucilage,15mg·kg^-1·d^-1）.Four weeks later,the rats were executed. The levels of plasma angiotensinⅡ（AngⅡ） in carotid common artery were detected by radioimmunoassay.Lumen cross section area（LA）,intraelastic layer area（IELA） and extraelastic layer area（EELA） were measured by computed video processing,and the ratio of（IELA-LA）/（EELA-IELA） was calculated.The expression of ACE 2 protein was determined by immunohistochemistry method.The expression of ACE 2 mRNA was evaluated by RT-PCR.Results （1） Compared with normal control,the hyperplasia of intima was markedly inhibited both in atorvastatin group and valsartan group（P〈0.01）.No change of media hyperplasia area was validated in all groups（P〉0.05）.（2） Compared with SHR control group,the level of AngⅡin carotid was decreased in atorvastatin and valsartan treatment group（P〈0.01）,whereas the level of plasma AngⅡ,the expression of ACE 2 mRNA and protein were raised markedly（P〈0.01）,and it＇s more obviously in valsartan treatment group（P〈0.05,P〈0.01）.Conclusion Atorvastatin could inhibit hyperplasia of intima in carotid common artery,which may be related to cut down the level of AngⅡin carotid artery,and upregulate the expression of ACE 2 mRNA and protein.