依达拉奉对大鼠心肌转化生长因子-β_1表达及心肌纤维化的影响

Effects of edaravone on the expression of TGF-β_1 and myocardialfibrosis in rats

目的观察依达拉奉抗大鼠心肌纤维化作用并探讨转化生长因子-β1(TGF-β1)表达水平与心肌纤维化的关联性。方法 40只雄性SD大鼠随机分为对照组、模型组和依达拉奉低、中、高剂量组。采用异丙肾上腺素(ISO)建立大鼠心肌纤维化模型。依达拉奉各剂量组予以依达拉奉[分别为3、5、10 mg/(kg·d)]干预14 d。第15天检测超氧化物歧化酶(SOD)活力、丙二醛(MDA)水平,计算左心室质量指数(LVMI)、胶原容积分数(CVF);采用免疫荧光和Western blot检测TGF-β1的表达。结果与对照组比较,模型组的MDA、LVMI均显著升高,而SOD显著降低(P<0.01)。与模型组比较,依达拉奉各剂量组随干预剂量增加,MDA表达递减,SOD表达递增(P<0.05);依达拉奉中剂量组SOD与对照组差异无统计学意义,而LVMI呈递减(P<0.01),依达拉奉高剂量组LVMI与对照组差异无统计学意义。模型组TGF-β1较对照组表达明显上调,依达拉奉各剂量组TGF-β1的表达随剂量的增加而减少,条带灰度减弱。模型组CVF较对照组显著增加;依达拉奉中、高剂量组CVF随剂量的增加而降低,但均高于对照组(P<0.01)。TGF-β1与MDA、LVMI、CVF呈正相关(r分别为0.931、0.879、0.930,P<0.001),与SOD呈负相关(r=-0.892,P<0.001)。结论依达拉奉具有通过减轻氧化应激水平和抑制TGF-β1表达而达到抗心肌纤维化作用。

Objective To investigate the effects of edaravone on myocardial fibrosis induced by isoproterenol （ISO） in rats, and to discuss the correlation between the level of transforming growth faetor-β1 （TGF-β1） and the myocardial fibrosis. Methods Forty male SD rats were randomly divided into five groups, namely control group, model group and edaravone groups （low, medium and high doses）. Isoproterenol was used to establish the rat model of myocardial fibrosis. Edaravone groups were given edaravone [3, 5 and 10 mg/（kg, d）] to intervene for 14 days. The activity of superoxide dismutase （SOD） and the level of malondialdehyde （MDA） were examined after 15-d treatment. The left ventricular mass index （LVMI） and collagen volume fraction （CVF） were examined. The expression of TGF-β1 was detected by Westem blot assay and immuno- fluorescence method. Results The content of MDA and LVMI were significantly higher in model group than those of the control group （P 〈 0.01）, whereas the content of SOD was significantly lower in model group than that of the control group （P 〈 0.01）. Compared with model group, the expression level of MDA decreased with the increased intervention dose of edara- vone （P 〈 0.05）, while SOD expression level increased （P 〈 0.05）. There was no significant difference in the level of SOD be- tween middle dose edaravone group and the control group. LVMI was decreased with the increased doses of edaravone （P 〈 0.01）. There was no significant difference in LVMI between the high dose of edaravone group and the control group. Com- pared with the control group, the expression level of TGF-β1 was significantly increased in model group （P 〈 0.01）. The ex- pression level of TGF- β1 was reduced with the increased doses of edaravone. CVF was significantly increased in model group compared with that of control group （P 〈 0.001）. CVF decreased with the increased doses of edaravone in medium and high doses of edaravone groups, but they were higher than that of control group （P 〈 0.01）. TGF-β1 was positively correlated with MDA, LVMI and CVF （r=0.931, 0.879 and 0.930, P 〈 0.001）. SOD was negatively correlated with TGF-β1, （r= -0.892, P 〈 0.001）. Conclusion Edaravone can relieve myocardial fibrosis by inhibiting oxidative stress and TGF-β1 in rats.