eNOS/PKG-1通路在L-精氨酸抗野百合碱所致大鼠右心室重构中的作用

Role of eNOS/PKG-1 pathway in L-Arginine against right ventricular remodeling induced by monocrotaline in rats

目的借助工具药L-NAME,探讨eNOS/PKG-1通路在L-精氨酸(L-Arginine,L-arg)干预野百合碱(monocrotaline,MCT)所致大鼠右心室重构的作用。方法20只SD大鼠随机分为4组,正常对照组、MCT组、L-arg组和L-arg+L-NAME组。观察大鼠一般状况;采用右心导管术检测大鼠右心室压;称大鼠体质量和右心室重量,计算右心室质量指数;HE染色观察大鼠右心室形态学变化;蛋白免疫印迹法检测右心室cTnI、eNOS和PKG-1蛋白的表达。结果与Control组相比,MCT组大鼠右心室最大压和右心室质量指数均明显升高(P<0.05),体质量明显减轻(P<0.05);右心室心肌细胞肥大,且排列紊乱;cTnI蛋白的表达明显上调(P<0.05),eNOS和PKG-1蛋白表达均明显下调(P<0.05)。L-arg能明显改善上述变化(P<0.05)。而eNOS抑制剂L-NAME能明显阻断L-arg的作用(P<0.05)。结论L-arg可改善MCT所致大鼠右心室重构,其机制可能与上调eNOS和PKG-1蛋白的表达有关。

Aim To investigate the role of eNOS/PKG-1 pathway in L-arginine(L-arg)intervention in right ventricular remodeling induced by monocrotaline(MCT)in Sprague Dawley(SD)rats with the aid of the tool medicine L-NAME.Methods Twenty SD rats were randomly divided into control group,MCT group,L-Arg group and L-Arg+L-NAME group.The general condition of rats was observed;the right ventricular pressure of rats was measured by right heart catheterization;the rats and the right ventricle were weighed and the right ventricular mass index was calculated;the morphological changes of the right ventricular were observed by H&E staining;the protein expressions of cTnI,eNOS and PKG-1 were detected by Western blot in the right ventricular.Results Compared with control group,right ventricular max pressure and right ventricular mass index significantly increased(P<0.05);the weight of rats in MCT group was significantly reduced(P<0.05);the right ventricular myocytes were hypertrophic,disordered and infiltrated with inflammatory cells;the protein expression of cTnI was obviously up-regulated(P<0.05);the protein expressions of eNOS and PKG-1 were significantly down-regulated(P<0.05).L-arg could significantly improve the above changes(P<0.05).However,the effects of L-arg were inhibited by eNOS inhibitor L-NAME.Conclusions L-arg can improve the right ventricular remodeling in rats induced by MCT,and the mechanism may be related to the up-regulation of the protein levels of eNOS and PKG-1.