耐力运动调控miR-378改善压力超负荷型心力衰竭大鼠心脏纤维化的机制研究  

Study on the mechanism of endurance exercise regulating miR-378 to improve cardiac fibrosis in rats with pressure overload-induced heart failure

作　　者：胡思远 熊霞军 钟森杰 黄淑敏 杨梦 李琳[3] 王世慧 王跃欢 逯平 胡志希[3] HU Siyuan;XIONG Xiajun;ZHONG Senjie(School of Sports Art,Hunan University of Chinese Medicine,Changsha,Hunan,410208)

机构地区：[1]湖南中医药大学体育艺术学院,湖南省长沙市410208 [2]武汉体育学院运动医学院 [3]湖南中医药大学中医诊断研究所 [4]湖南中医药大学针灸推拿与康复学院

出　　处：《中国康复医学杂志》2025年第2期180-187,共8页Chinese Journal of Rehabilitation Medicine

基　　金：湖南省自然科学基金项目(2020JJ5408);湖南省教育厅科学研究项目(21B0361);湖南中医药大学国自然预研项目(2024XJYY11);湖南省大学生创新创业训练计划项目(2021-2458);湖南中医药大学大学生创新创业训练计划项目(2020-118)。

摘　　要：目的:探讨运动改善心力衰竭(心衰)心脏纤维化的作用机制,阐明miR-378在耐力运动调节心脏纤维化中的作用。方法:选取24只SD大鼠随机分为手术组与假手术组(sham),采用主动脉弓缩窄术(TAC)复制心衰心脏纤维化的大鼠模型,sham组只穿针不结扎。大鼠成模后再随机分为模型组(TAC)与运动组(Ex)。Ex组采用6周游泳耐力运动,干预结束后对各组大鼠进行超声心动图和病理形态学分析,ELISA法检测血清N末端B型利钠肽前体(NTproBNP)浓度,Western Blot法与qPCR法检测心脏组织α-平滑肌肌动蛋白(α-SMA)、Ⅰ型胶原(ColⅠ)、Ⅲ型胶原(ColⅢ)、转换生长因子β1(TGF-β1)、miR-378、TGF-β1 mRNA、COL1A1、COL3A1表达。结果:与sham组比较,TAC组左室射血分数(LVEF)、左室短轴缩短率(LVFS)、每搏输出量(SV)明显下降(P<0.05),左室舒张末期容积(EDV)、左室收缩末期容积(ESV)无显著性差异(P>0.05),血清NT-proBNP浓度显著上升(P<0.01);病理染色显示心肌细胞明显水肿,排列紊乱,胶原容积分数(CVF)显著升高(P<0.01);心脏组织纤维化相关因子α-SMA、ColⅠ、ColⅢ、TGF-β1、TGF-β1 m RNA、COL1A1、COL3A1表达显著上调(P<0.05),miR-378表达显著下调(P<0.01)。与TAC组比较,Ex组LVEF、LVFS、SV明显上升(P<0.05),左室收缩期内径(LVIDs)、ESV显著降低(P<0.01),NT-proBNP浓度下降(P<0.05);CVF显著降低(P<0.05);心脏组织中ColⅠ、ColⅢ、COL1A1、COL3A1的表达显著降低(P<0.05),miR-378表达升高(P<0.05),TGF-β1蛋白与mRNA表达降低(P<0.05)。结论:TAC能较好的复制压力超负荷型心衰心脏纤维化模型,耐力运动可以上调miR-378的表达,有效改善心脏纤维化水平,减缓心衰程度,恢复心功能,而这种作用机制可能与运动调控miR-378抑制心脏成纤维细胞活化有关。Objective:To explore the mechanism of exercise on improving cardiac fibrosis in heart failure,and the role of miR-378 in regulating Cardiac fibrosis by endurance exercise.Method:Twenty-four SD rats were selected and used transverse aortic constriction(TAC)to replicate the rat model of heart failure with cardiac fibrosis.They were randomly divided into the sham group,the TAC group and the exercise group.The exercise group performed swimming endurance exercise for 6 weeks.After training,the rats in each group were analyzed by echocardiography and pathological morphology,and the serum NT-proBNP concentration was detected by ELISA.Western Blot and qPCR were used to detect the expression ofα-SMA,ColⅠ,ColⅢ,TGF-β1,miR-378,TGF-β1 mRNA,Col1a1,and Col3a1 in heart tissue.Result:Compared with the sham group,left ventricular ejection fraction(LVEF),left ventricular short-axis shortening(LVFS),and output per beat(SV)were significantly decreased(P<0.05)in TAC group,and there were no significant differences in left ventricular end-diastolic volume(EDV)and left ventricular end-systolic volume(ESV)(P>0.05),and the serum NT-proBNP concentration was increased significantly(P<0.01).Pathological staining in TAC group showed that cardiomyocytes were obviously edematous and disorganzied,and collagen volume fraction(CVF)was significantly increased(P<0.05);the expression of fibrosis-related factorsαSMA,ColⅠ,ColⅢ,TGF-β1,TGF-β1 mRNA,Col1a1 and Col3a1 was significantly up-regulated(P<0.05),and the expression of miR-378 was significantly down-regulated(P<0.05).Compared with the TAC group,in the Ex group,LVEF,LVFS,SV increased significantly(P<0.05),LVIDs,ESV decreased significantly(P<0.01),NT-proBNP concentration decreased(P<0.05);CVF decreased significantly(P<0.05).The expressions of ColⅠ,ColⅢ,Col1a1 and Col3a1 in heart tissues were significantly reduced(P<0.05),α-SMA was not significantly different,and the expression of miR-378 increased(P<0.05).The expression of TGF-β1 and mRNA was reduced(P<0.05).Conclusion:TAC can bett

关 键 词：耐力运动 miR-378 心力衰竭 心脏纤维化 

分 类 号：R493[医药卫生—康复医学] R541.6[医药卫生—临床医学]