苦参碱对自发性高血压大鼠心肌间质纤维化的作用和机制

Effects and mechanisms of matrine on myocardium fibrosis in spontaneously hypertensive rat

目的:探讨苦参碱对自发性高血压大鼠(SHR)心肌间质纤维化的影响。方法:SHR 18只,随机分为SHR组(蒸馏水,10 m l/kg.d)、M at组(氧化苦参碱,100 mg/kg.d)、Bena组(苯那普利,10 mg/kg.d)。并以8周龄WKY组(蒸馏水,10 m l/kg.d)为阴性对照组。于给药前及给药8周后采用tail-cuff分别测量各组血压变化情况,给药8周后处死各组动物取血以及心脏,心脏称重,测量左心室质量指数(LVM I);放免法、ELISA法测血清Ⅲ型胶原(PCⅢ)、层粘蛋白(LN)及转化生长因子(TGFβ1)含量。心肌组织做HE、M asson染色及Ⅲ型胶原(ColⅢ)免疫组化检测,应用图像分析系统进行免疫组化半定量分析。结果:苦参碱显著减轻心肌间质纤维化(P<0.05)。苦参碱可显著降低血清PCⅢ、LN、TGFβ1,抑制心肌ColⅢ表达(P<0.05)。结论:苦参碱具有抗心肌间质纤维化的作用,这种作用与其降低循环中TGFβ1水平有关。

AIM： To study the effects of Matrine on myocardial fibrosis in spontaneously hypertensive rat （SHR）. METHODS： SHRs of 8-week-old were randomly divided into 3 groups ：SHR（water, 10 ml/kg · d） ,Mat （matrine, 100 mg/kg · d）, Bena （Benapril, 10 mg/kg · d） ,each group consisting of 6 rats. And 6 normal WKY rats were used as negative control. One day before and after 8-week treatments, we measured the SBP ,determined the LVMI; We also observed the change of structure and shape in the myocardial cells with masson, observed the expression of Colin with immunohistochemistry; we determined the levels of serum LN and PC m and the level of serum TGF-β1 with radioimmunoassay technique. RESLUTS： （1）Compared with WKY rats, the SBP, LVMI of SHR Were significantly increased. After the treatment of Benapril, the SBP, LVMI of SHR were significantly decreased. After the treatment of Matrine, the SBP, LVMI had no significant change. （2）Compared with WKY rats, the myocardial ColⅢ, serum PC Ⅲ, LN were significantly increased. After treatment of Benapril, the myocardial ColⅢ, serum PCⅢ, LN were significantly decreased. After the treatment of Matine, myocardial ColⅢ, serum PCⅢ, LN were significantly decreased. （3）Compared with WKY,the serum level of TGF-β1 in SHR were significant increased. After treatment of Benapril, the serum level of TGF-β1 in SHR were significantly decreased. After the treatment of Marine serum level of TGF-β1 in SHR were significantly decreased. CONCLUSION： Although Matrine can not decrease blood pressure and inhibit myocardial hypertrophy, it effectively decreases myocardial ColⅢ, serum PCⅢ ,LN by decreasing serum TGF-β1.