游泳运动通过TGF-β1/Smad3通路改善自发性高血压大鼠心肌间质纤维化研究

Improving Myocardial Interstitial Fibrosis of Spontaneously Hypertensive Rats through TGF-beta1/Smad3 Pathway by Swimming

目的:观察游泳运动对自发性高血压大鼠心肌间质形态学及TGF-β1/Smad3信号通路的影响。方法:选取8只SPF级雄性WKY大鼠为正常对照组(C组); 20只SPF级自发性高血压大鼠随机分为模型组(H组)和SHR+运动组(EH组),每组均10只,各组大鼠给予普通饲料喂养。运动组大鼠进行为期12周不负重游泳训练,每周训练6天,休息1天。第1周为适应性训练,从第2周开始维持60 min/d的运动时间至12周结束。干预周期结束后检测检测各组大鼠CVF%、col I和col III; QRT-PCR检测心肌Smad3,放免法检测Ang II,Western-blot法检测NOX2、TGF-β1、HSP90蛋白表达。结果:(1) C组比较,H组大鼠心肌CVF%、col I、col III、血浆Ang II、心肌Ang II、心肌NOX2、TGF-β1、Smad3mRNA、HSP90表达显著性增加(P <0. 05或P <0. 01);与H组比较,EH组大鼠除了心肌HSP90蛋白表达显著性增加外(P <0. 05),其余指标均显著性降低(P <0. 05或P <0. 01)。结论:游泳运动能较好降低SHR大鼠心肌col I和col III蛋白表达水平,改善心肌间质纤维化,主要通过降低Ang II介导NOX2表达,抑制下游TGF-β1/Smad3通路激活,其中HSP90作为其上游因子,在其中可能起着重要的调节作用。

Objective ： To observe the effects of swimming on TGF - beta1/Smad3 signaling in the ameriation process of myocardial interstitial remodeling of spontaneously hypertensive rats. Methods ： SPF male WKY rats were chosen as group C （ n = 8）, and SPF spontaneously hypertensive rats were divided into group model control （group H）, group SHR ＋ exercise （group EH）. The number of each group was 10. Rats in each group were fed on ordinary food. Exercise group rats were arranged to no -load swimming training for 12 weeks, and 6 days a week. Fitness training for 1 week before formal training. Rats arraged to swim 60rain per day from week 2 to 12 weeks. CVF% ,colⅠ and colⅢ were tested by Immunohistochenlistry, myocardial Smad3 by QRT - PCR, and NOX2, TGF - beta 1, HSP90 protein expression by western - blot. Results ： （ 1 ） Compared with group C, myocardial CVF %, colⅠ, colⅢ protein expression, blood plasma AngⅡ, myocardial AngⅡ, myocardial NOX2 protein expression, TGF- beta1 protein expression , Smad3mRNA level and HSP90 protein expression in rats group SHR significantly increased （P 〈 0.05 or P 〈 0.01 ） ; （2） Compared with group SHR, 12 -week swimming could significantly reduce myocardial CVF% ,colⅠ, colⅢ protein expression ,plasma AngⅡ, myocardial AngⅡ ,NOX2 protein expression, TGF - beta 1 protein expression and Smad3 mRNA （ P 〈 0.05 ） ,increase HSP90 protein expression （ P 〈 0.05 ）. Conclusions ： Swimnling could reduce colⅠ and colⅢ protein expression in hearts of SHR, ameliorate myocardial interstitial fibrosis, mainly by reducing AngⅡ mediated NOX2 protein expression, and inhibiting downstream TGF - beta1/Smad3 pathways, in which HSP90 as its upstream factor may play an important role.