抗心肌纤维化治疗家兔慢性心力衰竭的实验研究

目的 探讨姜黄素的抗心肌纤维化作用对家兔慢性心力衰竭(心衰)的影响.方法 30只新西兰大耳白兔随机分为对照组、心衰组、姜黄素组,每组10只.心衰组和姜黄素组采用主动脉瓣反流及主动脉缩窄法制作心衰模型,对照组做假手术但不造成主动脉瓣反流和主动脉缩窄.姜黄素组口服姜黄素(100 nag·kg-1·d-1),对照组和心衰组口服安慰剂.主动脉瓣反流术及其假手术前,主动脉缩窄术及其假手术后8周,所有动物做2次心脏超声检查.第2次超声检查后,取出心脏行基质金属蛋白酶(MMP)-2和MMP-9的免疫组织化学染色和Masson染色,观察MMP表达的改变和心肌纤维化情况.结果 前后2次超声结果 比较,心衰组左室射血分数和左室内径缩短分数显著下降,左室内径、左室后壁和室间隔厚度显著增大;姜黄素组上述指标也有显著改变,但程度较心衰组轻;对照组上述指标无显著改变.Masson染色显示,心衰组胶原含量高于姜黄素组和对照组(P<0.05);免疫组织化学染色显示,心衰组MMP-2和MMP-9的表达低于姜黄素组和对照组(P<0.05).结论 姜黄素通过提高MMP的表达可减轻心衰时的心肌纤维化,该作用可能是其改善心衰时心肌重构和心脏收缩功能的重要机制之一.抗纤维化治疗有可能成为心衰治疗的新方法 .

Curcumin attenuates left ventricular dysfunction and remodeling in rabbits with chronic heart failure

Objective To investigate the effects of Curcumin on rabbits with chronic heart failure. Methods Heart failure was induced by combined aortic regurgitation and aortic stenosls in 20 New for 8 weeks, 10 sham operated rabbits served as controls (Con). Echocardiography was performed in all rabbits at baseline and 8 weeks later. Aortic diameter (AO), left ventricular ejection fraction (LVEF), left ventricular fractional shortening ( LVFS), left ventricular end-systolic dimension (LVDs), left ventricular end-diastolic dimension ( LVDd), left ventricular posterior wall thickness (LVPW) and interventricular septum thickness (IVS) were measured. Myocardial matrix metalloproteinase (MMP)-2 and MMP-9 expressions and fibrosis were determined by immunohistochemistry and Masaon staining respectively. Results Compared to baseline, LVEF and LVFS were significantly decreased, AO, LVDs, LVDd, LVPW, and IVS significantly increased at 8 weeks after operation in HF group hile these changes could be significantly attenuated in Curcumin treated rabbits. The protein expressions of MMP-2 and MMP-9 were significantly down-regulated in HF group and could be significantly up-regnlated by Curcumin treatment. The increased collagen deposition in HF group was also significantly reduced by Cureumin treatment. Conclusion Curcumin attenuated left ventricular dysfunction and remodeling by up-regulating MMPs expressions and reducing myocardial fibrosis.