丹参酮ⅡA对压力负荷增加大鼠心肌纤维化的改善作用

Improvement of Tanshinone ⅡA on Myocardial Fibrosis in Rats with Pressure Overload

目的:观察丹参酮ⅡA(TanⅡA)对压力负荷增加大鼠心肌纤维化的改善作用。方法:60只SD大鼠随机分为假手术组(Sham组,n=8)和手术组(n=52),手术组均行腹主动脉缩窄术制备压力负荷增加心肌纤维化模型,术后4周,存活的32只成模大鼠中8只留作模型组(Model组),余24只分为TanⅡA低剂量组(L-TanⅡA组,10mg/Kg/天)、TanⅡA高剂量组(H-TanⅡA组,20mg/Kg/天)及阳性对照药物卡托普利组(Captopril组,100mg/Kg/天),每组8例。给药4周后,检测5组大鼠心肌肥厚指数和心肌组织形态、心肌羟脯氨酸(HYP)含量、心肌组织Rho相关卷曲螺旋蛋白激酶1(ROCK1)、转化生长因子-β1(TGF-β1)和核转录因子-κBp65(NF-κBp65)蛋白含量。结果:与Sham组比较,Model组大鼠的心肌肥厚指数、心肌HYP含量及心肌组织中ROCK1、TGF-β1和NF-κBp65蛋白含量均显著升高(P均<0.01),组织病理学改变明显;与Model组比较,L-TanⅡA和H-TanⅡA组心肌肥厚指数、心肌HYP含量及心肌组织中ROCK1、TGF-β1和NF-κBp65蛋白含量均降低(P<0.05或P<0.01),组织病理学改变明显。结论:TanⅡA能改善压力负荷增加大鼠心肌纤维化,此作用可能与其抑制ROCK1表达,下调TGF-β1和NF-κBp65水平有关。

Objective: To observe the improvement of tanshinone ⅡA (TanⅡA) on myocardial fibrosis in rats with pressure overload. Method: 60 Sprague-Dawley (SD) rats were randomly divided into sham operation group (sham group,n=8) and surgical group (n=52). The rats of surgical group induced by the abdominal aorta constriction preparation. 32 rats of surgical group survived and were randomly divided into four groups (n=8):model group, TanⅡA low dose group (L-TanⅡA group), TanⅡA high dose group (H-TanⅡA group) and positive captopril group (captopril group). After 4 weeks, heart mass indexes were estimated, in concurrent evaluation of myocardial histology, as well as myocardial hydroxyproline content by ELISA, and immunohistochemistry staining for myocardial ROCK1, transforming growth factor-beta1 (TGF-β1) and nuclear transcription factor-kappa B p65 (NF-κB p65) protein content. Results: Compared with those in sham group, heart mass indexes, myocardial hydroxyproline content and myocardial ROCK1, TGF-β1 and NF-κB p65 content were increased in the model group (P<0.01); Compared with those in model group, heart mass indexes, myocardial hydroxyproline content and myocardial ROCK1, TGF-β1 and NF-κB p65 content were decreased in the L-TanⅡA group (P<0.05 or P<0.01), while these indexes were decreased significantly in the H-Tan Ⅱ A group (P<0.01). Conclusion: TanⅡA can improve myocardial fibrosis in rats with pressure overload and this effect may be related to inhibition of ROCK1 expression, downregulation of TGF-β1 and NF-κB p65 expression.