miR-21对运动性右室心肌纤维化发生的影响

Effects of MiR-21 on Exercises-induced Right Ventricularfibrosis

目的:研究在长期大强度运动引起的右室心肌纤维化中miR-21表达水平的变化,探讨miR-21在运动性心肌纤维化中的作用。方法:72只雄性SD大鼠,随机分为安静对照组(Sed,n=24)、中强度运动组(ME,n=24)和大强度运动组(IE,n=24),每组按照训练周期又分为8周、12周和16周,各8只。安静对照组自由活动,中强度组和大强度组分别以速度15.2 m/min、坡度5°和速度28 m/min、坡度10°的条件每天运动1 h,每周运动5天。各组最后一次运动结束24小时后,下腔静脉采血并处死,迅速分离心脏取右心室。天狼星红染色测定右心室的胶原容积分数(CVF);免疫荧光检测Ⅰ胶原蛋白(ColⅠ)的含量;RT-PCR检测miR-21的表达水平。结果:12周(P<0.05,P<0.05)和16周(P<0.01,P<0.01)大强度运动后大鼠右室心肌胶原容积分数显著高于安静对照组与中强度运动组;与安静对照组和中强度运动组比,12周(P<0.01,P<0.01)和16周(P<0.01,P<0.01)大强度运动使右室Ⅰ胶原蛋白的含量显著增多。与安静对照组相比,8周、12周和16周大强度运动都可使大鼠miR-21表达水平显著升高(P<0.01、P<0.05和P<0.05),且在16周时miR-21的表达水平与Ⅰ胶原蛋白的含量正相关(r=0.443,P=0.03)。结论:长期大强度运动后右室心肌纤维化与miR-21表达水平增高有关,miR-21是潜在的运动性心肌纤维化的新生物标志物和干预靶点。

Objective To explore the expression level of miR-21 in exercise-induced right ventricular （RV） fibrosis,and to analyze the role of miR-21 in exercise-induced right ventricular fibrosis. Meth- ods Seventy-two male Sprague-Dawley rats were randomly divided into a sedentary （Sed） group,a moderate exercise （ME） group and an intensive exercise （IE） group,each of 24. Rats in the Sed group were free of exercises,while those in ME and ]E groups ran an hour on treadmill at 5°and 10° slopes at the speed of 15.2 m/min and 28 m/min respectively for 8 weeks, 12 weeks or 16 weeks every day, 5days per week. Twenty-four hours after the last training,all rats were sacrificed after blood sampling. The right ventricles were removed,and the collagen volume fraction （CVF） was tested using Sirius red staining, Collagen I （Col I ） content was quantified using Immunofluorescence. The expression level of miR-21 was measured using the reverse transcription-polymerase chain reaction （RT-PCR）. Results After 12 weeks （P〈0.05,P〈0.05） and 16 weeks （P〈0.01,P〈0.01） of intensive exercises, the average CVF in the right ventricular was significantly higher than that of Sed and ME rats. Compared to Sed and ME groups,12 weeks （P〈0.01,P〈0.01） and 16 weeks （P〈0.01,P〈0.01） of intensive exercises significantly increased RV collagen I content. Compared to the Sed group,the expression of miR-21 in RV increased significantly in the IE group （P〈0.01,P〈0.05 and P〈0.05）. After 16-week intensive exercises, the miR-21 expression was positively correlated with the RV Col I content. Conclusion The right ventricular fibrosis induced by long-term intensive exercises is associated with increased miR-21 expression level. Therefore,miR-21 is a potent therapeutic target and novel biomarker of the exercise- induced right ventricular fibrosis.