丹参酮ⅡA对压力负荷增加大鼠心肌纤维化的影响  

Effect of tanshinone ⅡA on myocardial fibrosis in rats with pressure overload

作　　者：蔡辉[1] 常文静[1] 赵凌杰[1] 赵智明[1] 董晓蕾[1] 沈思钰[1] 

机构地区：[1]南京军区南京总医院中西医结合科,210002

出　　处：《中华老年心脑血管病杂志》2013年第12期1307-1311,共5页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

摘　　要：目的探讨丹参酮(Tan)ⅡA对压力负荷增加大鼠心肌纤维化的影响。方法选择SD大鼠60只,采用腹主动脉缩窄术制备压力负荷增加大鼠心肌纤维化模型,动脉夹闭4周后,将存活大鼠40只随机分为假手术组、模型组、TanⅡA低剂量组[L-TanⅡA组,10mg/(kg·d)]、TanⅡA高剂量组[H-TanⅡA组,20mg/(kg·d)]及阳性对照药物卡托普利组[卡托普利组,100mg/(kg·d)],每组8只。8周末检测心脏质量指数、左心室质量指数、心肌组织病理学、心肌羟脯氨酸含量、心肌同组基因蛋白A(RhoA)、Rho激酶1(ROCK1)、结缔组织生长因子和血清TNF-α蛋白的水平。结果与假手术组比较,模型组大鼠心脏质量指数、左心室质量指数、羟脯氨酸、RhoA、ROCK1、结缔组织生长因子和TNF-α蛋白水平明显升高,差异有统计学意义(P<0.05,P<0.01);与模型组比较,L-TanⅡA组和H-TanⅡA组上述各项指标明显下降,差异有统计学意义(P<0.05,P<0.01)。结论 TanⅡA可能通过抑制RhoA/ROCK信号通路,降低下游炎性细胞因子和促纤维化细胞因子分泌,从而减少压力负荷增加大鼠心肌炎性反应和纤维化,为心肌纤维化的治疗提供新的依据。Objective To study the effect of tanshinone Ⅱ A （Tan ⅡA） on myocardial fibrosis in rats with pressure overload. Methods Sixty SD rats were included in this study. A myocardial fibrosis model of rats with pressure overload was established by abdominal aorta constriction. Four weeks after abdominal aorta occlusion,40 surviving rats were randomly divided into sham opera- tion group,model group,low TanⅡA dose [10 mg/（kg ·d）] group,high Tan ⅡA dose [20 rag/ （kg·d）] group and positive captopril [100 mg/（kg ·d）] group （8 in each group）. Their cardiac mass index, left ventricular mass index, myocardial histology, and myocardial hydroxyproline （HYP） ,RhoA,ROCK1,CTGF and serum TNF-a were measured at week 8 after the model was established. Results The cardiac mass index,left ventricular mass index,and myocardial HYP, RhoA,ROCK1 ,CTGF,serum TNF-a were significantly higher in model group than in sham oper- ation group and significantly lower in low Tan ⅡA dose group and high Tan ⅡA dose group than in model group （P〈0.05,P〈0.01）. Conclusion Tan ⅡA can reduce the secretion of down- stream inflammatory factors and fibrogenic cytokines by inhibiting the RhoA/ROCK signaling pathway,thus reducing the pressure overload, activated inflammation and fibrosis of myocadial tissue, and providing the novel evidence for the treatment of myocardial fibrosis.

关 键 词：心内膜心肌纤维化症 RHO相关激酶类 结缔组织 肿瘤坏死因子A 细胞外基质 丹参酮 

分 类 号：R285.5[医药卫生—中药学]