GCIP-27对自发性高血压大鼠左心室结构影响的实验研究

目的观察GCIP-27连续给药对自发性高血压大鼠(SHR)左心室结构的影响。方法30只SHR随机分为5组。空白溶剂对照组、阳性对照氯沙坦组(6mg·kg-1)和GCIP-27(10、30、90μg·kg-1ip,bid)3组,另6只Wistar-Kyoto大鼠(WKY)作为正常对照组。药物干预8wk后,测定SHR收缩压(SBP)、心室重量指数,分别用光镜、透射电镜观察心肌结构;VG染色测定心肌间质胶原含量。结果用药后第2周开始,SHR各剂量组(GCIP-2710、30、90μg·kg-1)SBP明显低于空白对照组(P<0·05);心肌重量指数(HMI)和左心室肥厚指数(LVMI)均明显降低(P<0·05);心肌间质胶原面积(CA)、胶原含量(IOD)及胶原容积分数(CVF)均明显减少(P<0·01)。光镜及电镜显示GCIP-27能明显改善SHR的心肌病理改变及超微结构。结论GCIP-27能明显改善SHR的心脏结构,降低心肌间质胶原增生,同时发挥降血压作用,进而对SHR左室重构的形成发挥干预及保护作用。

Effects of GCIP-27 on the structure of left ventricle in spontaneously hypertensive rats

Aim To observe the effects of GCIP-27(G protein competitive inhibitory polypeptide-27) on the structure of left ventricle in spontaneously hypertensive rats(SHR).Methods Thirty SHR rats of 12 weeks old were randomly divided into five groups(n=6):blank control groups,GCIP-27(10,30,90 μg·kg-1,ip,bid)groups,and Losartan group(6 mg·kg-1),six Wistar-Kyotos(WKY) rats were as normal control.Systolic blood pressure(SBP)was measured once per two weeks with tail-sleeve methods.At the end of the 8th week,left ventricle weight index(LVWI)were determined.Myocardium structure was observed by polaroscope and transmission electron microscope.The area and content of myocardial interstitial collagen were treated for semiquantitative analysis by image analyzer system.Results The SBP in GCIP-27(10,30,90 μg·kg-1)groups decreased significantly from the 2 nd to the 8th week by comparison with blank control group.GCIP-27(10,30,90 μg·kg-1) lowered heart mass index(HMI)and left ventricular mass index(LVMI)markedly compared with blank control group(P<0.05).Collagen area(CA),integral optic density(IOD)and collagen volume fraction(CVF)of myocardial interstitial in the GCIP-27(10,30,90 μg·kg-1)groups were lowered compared with those in the control group(P<0.01).GCIP-27 was more obvious in improving myocardial ultrastructure and pathology such as hypertrophy and degeneration.Conclusions GCIP-27 plays a preventive and protective role in the development of left ventricular remodeling of spontaneously hypertensive rats.It can improve the myocardial structure,attenuate the hyperplasia of collagen markedly,and reduce the blood pressure as well.