xy9902抗大鼠心肌重构作用的实验研究

目的研究新型选择性雌激素受体调节剂(SERMs)xy9902对大鼠心肌重构的干预作用,并初步探讨其机制。方法腹主动脉缩窄复制压力负荷增高致大鼠心肌重构动物模型,术后2周存活动物分为模型组(AAC)、卡托普利组(Cap)及xy9902组(xy9902),另设假手术组(Sham)。Mal-lory三色染色观察心肌组织胶原纤维含量的变化。黄嘌呤氧化酶法测定心肌组织SOD活性,硫代巴比妥酸法测定MDA含量。结果与Sham组比较,AAC组心脏指数HMI及LVMI增加,心肌细胞排列紊乱、增粗,细胞间隙明显增宽,可见大量异常胶原纤维堆积,CVF增大,然而Cap组和xy9902组明显好转。AAC组心肌SOD活性下降,MDA含量增加,Cap组和xy9902组与AAC组比较,SOD活性增加,MDA含量下降(P<0.01)。相关分析结果表明CVF与SOD/MDA比值呈负相关(P<0.01)。结论 xy9902对心肌重构有防治作用,其对体内氧化应激平衡的正向调控可能是抗心肌重构的分子机制之一。

Experimental study of xy9902 on rat myocardial remodeling

Aim To investigate the effects and mechanisms of xy9902 on myocardial remodeling induced by pressure overload in rats.Methods Abdominal aortic constriction(AAC) method was applied to establish myocardial remodeling models.Captopril(10 mg·kg-1·d-1) and xy9902(10 mg·kg-1·d-1) were administered intragastrically for treatment.Collagen content in myocardium was determined by reforming Mallory’s staining.Superoxide dismutase(SOD) activity and malonicdialdehyde(MDA) content were determined by xanthine oxidase and 2-thiobarbituric acid respectively.Results Myocardial cells distributed disorder,filaments breakage,and collagen hyperplasia in AAC group,but these phenomenon turned to better in Captopril and xy9902 groups.Compared with sham group,SOD activity was down-regulated but MDA content was up-regulated in AAC group(P<0.01);however,SOD activity was up-regulated but MDA content was down-regulated in Captopril and xy9902 groups(P<0.01).Furthermore,Correlation analysis showed that CVF was negatively correlated with the ratio of SOD/MDA(r=-0.801,P<0.01).Conclusion Xy9902 can prevent myocardial remodeling,and the disproportion of SOD and MDA may be one of the molecular mechanisms.