肌肉质量对腹主动脉缩窄大鼠心脏结构和功能的影响OA北大核心CSTPCD
Effect of muscle mass on cardiac structure and function in rats with ab-dominal aortic constriction
目的:探究骨骼肌质量对腹主动脉缩窄(AAC)大鼠心脏结构和功能的影响及可能机制.方法:(1)雄性SD大鼠30只,随机分为对照(CON)组、肌萎缩(MA)组和肌肥大(MH)组,每组10只.MA组通过去除后腿两侧胫神经构建双下肢MA模型,MH组通过负重跑构建MH模型.4周后取材,测定MA和MH指标.(2)在以上模型构建完成的基础上,另取大鼠随机分为CON组、心肌病理性重构组(AAC组)、MA+AAC组和MH+AAC组,每组10只.对AAC组、MA+AAC组和MH+AAC组大鼠进行AAC手术,CON组进行假手术.术后4周超声检测心脏结构和功能;病理染色观察比目鱼肌、腓肠肌和心肌形态学改变;ELISA法检测血清肌生成抑制蛋白(MSTN)浓度;real-time PCR检测心肌组织心房钠尿肽(ANP)和脑钠肽(BNP),以及骨骼肌和心肌组织MSTN的mRNA表达水平.结果:4周的去神经术或负重跑训练后,与CON组相比,MA组大鼠腓肠肌和比目鱼肌显著萎缩,MH组大鼠腓肠肌和比目鱼肌显著肥大,但两组心重/体重、左室舒张末期心室壁厚度、射血分数等相关指标均无显著差异(P>0.05).与AAC组相比,MA+AAC组大鼠心重/体重和左室舒张末期心室壁厚度显著增大,舒张末期内径显著降低,射血分数显著上升(P<0.05或P<0.01),心肌纤维化加重;MH+AAC组心重/体重和左室舒张末期心室壁厚度显著降低,舒张末期内径显著增加,射血分数显著降低(P<0.05或P<0.01),心肌纤维化减轻.与AAC组相比,MA+AAC组心肌ANP和BNP的mRNA表达水平显著上升,MH+AAC组ANP和BNP的mRNA表达水平显著下降(P<0.01).与AAC组相比,MA+AAC组比目鱼肌、腓肠肌和心肌MSTN的mRNA表达水平,以及血清MSTN含量均显著上升(P<0.01);MH+AAC组腓肠肌和心肌MSTN的mRNA表达水平,以及血清MSTN含量均显著下降(P<0.05).结论:萎缩的骨骼肌加重AAC手术诱导的心脏病理性重构,而肥大的骨骼肌使AAC诱导的病理性重构减轻.骨骼肌质量对心脏病理性重构有着重要影响.MSTN可能参与了骨骼肌质量对心脏病理性重构的调节.
AIM:To investigate the effects of skeletal muscle mass on cardiac structure and function in rats subjected to abdominal aortic constriction(AAC),and to explore its potential mechanisms.METHODS:(1)Thirty male SD rats were randomly divided into 3 groups:control(CON)group(n=10),muscular atrophy(MA)group(n=10),and muscular hypertrophy(MH)group(n=10).The rats in MA group underwent bilateral tibial nerve removal to induce MA,while those in MH group engaged in weight-bearing running to promote MH.Four weeks later,skeletal muscle sam-ples were collected,and indicators of MA and MH were assessed.(2)Another rats after modeling above were divided into 4 groups:CON group(n=10),cardiac pathological remodeling group(AAC group;n=10),MA+AAC group(n=10),and MH+AAC group(n=10).All rats,except those in CON group which underwent a sham operation,received AAC sur-gery.Four weeks after surgery,cardiac structure and function were assessed by echocardiography,while morphological changes of the soleus and gastrocnemius muscles and myocardium were evaluated by pathological staining.Serum myo-statin(MSTN)level was measured using ELISA.The mRNA expression levels of atrial natriuretic peptide(ANP)and brain natriuretic peptide(BNP)in the myocardium,and MSTN in the skeletal muscle and myocardium were detected by real-time PCR.RESULTS:After 4 weeks of either denervation or weight-bearing running,significant atrophy and hyper-trophy of the gastrocnemius and soleus muscles were observed in MA and MH groups,respectively,compared with CON group.However,no significant differences were noted in heart weight/body weight ratio,left ventricular end-diastolic wall thickness,ejection fraction,or other related indexes among these groups(P>0.05).In comparison to AAC group,the rats in MA+AAC group showed a significant increase in heart weight/body weight ratio and left ventricular end-diastolic an-terior wall thickness,a decrease in end-diastolic internal diameter,an increase in ejection fraction(P<0.05 or P<0.01),and exacerbated myocardial fibrosis.Conversely,in MH+AAC group,there was a significant decrease in heart weight/body weight ratio and left ventricular end-diastolic wall thickness,an increase in end-diastolic internal diameter,and a lower ejection fraction(P<0.05 or P<0.01),with reduced myocardial fibrosis.Compared with AAC group,myocardial ANP and BNP mRNA expression significantly increased in MA+AAC group and decreased in MH+AAC group(P<0.01).Additionally,soleus and gastrocnemius muscle MSTN mRNA expression,myocardial MSTN mRNA expression,and se-rum MSTN level significantly increased in MA+AAC group(P<0.01)and significantly decreased in MH+AAC group(P<0.05).CONCLUSION:Atrophic skeletal muscle exacerbated the pathological remodeling induced by AAC surgery,whereas hypertrophic skeletal muscle mitigated this remodeling.Skeletal muscle mass plays a critical role in cardiac patho-logical remodeling,with MSTN potentially regulating this process.
李世田;陈雪飞;邢正;郭兰兰;张靓
北京师范大学体育与运动学院,北京 100875郑州大学体育学院,河南 郑州 450052对外经济贸易大学体育部,北京 100875
临床医学
心血管疾病骨骼肌肌萎缩肌肥大腹主动脉缩窄肌生成抑制蛋白
cardiovascular diseasesskeletal musclemuscular atrophymuscular hypertrophyabdominal aorta constrictionmyostatin
《中国病理生理杂志》 2024 (007)
1153-1162 / 10
国家自然科学基金资助项目(No.31871207)
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