昼夜节律紊乱通过影响心肌脂代谢对心肌梗死后心脏重构影响机制的相关性研究  

CRD affects post-infarction cardiac remodeling through influencing myocardial lipid metabolism:a mechanistic study

作　　者：胡睿杰 矫鹂莹 谭伍平 江洪[1] Hu Ruijie;Jiao Liying;Tan Wuping;Jiang Hong(Department of Cardiology,Renmin Hospital of Wuhan University,Wuhan 430060,Hubei Province,China)

机构地区：[1]武汉大学人民医院心血管内科、武汉大学心脏自主神经研究中心、武汉大学心血管病研究所、心血管病湖北省重点实验室,430060

出　　处：《中华老年心脑血管病杂志》2024年第4期440-444,共5页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：国家自然科学基金(81970287)。

摘　　要：目的探究昼夜节律紊乱是否加重心肌梗死(MI)后心脏重构及潜在的脂代谢相关机制。方法选取18只健康SPF级雄性SD大鼠,随机分为假手术(sham)组、MI组和昼夜节律紊乱(MI+Dis)组,每组6只。适应性饲养14 d后,MI组和MI+Dis组建立MI模型,MI+Dis组接受24 h持续光照7 d建立昼夜节律紊乱模型。用超声心动图评估心脏功能,苏木精-伊红染色检测MI诱导的心肌损伤,Masson染色检测心肌胶原纤维表达,免疫荧光检测心肌纤维化标志物α平滑肌肌动蛋白(α-SMA)表达,逆转录聚合酶链反应法检测肉碱棕榈酰转移酶1β(CPT-1β)、过氧化物酶体增殖物激活受体α(PPARα)、心肌胶原组织Ⅰ型(CollagenⅠ)和心肌胶原组织Ⅲ型(CollagenⅢ)的信使RNA(mRNA)表达水平,生化法检测血清三酰甘油(TG)、总胆固醇(TC)水平。结果与sham组比较,MI组大鼠左心室收缩末期内径(LVESD)、左心室舒张末期内径(LVEDD)、心肌α-SMA、CollagenⅠ、CollagenⅢ相对表达量显著升高(P<0.05,P<0.01),左心室射血分数(LVEF)和左心室短轴缩短率(LVFS)显著降低(P<0.05);与MI组比较,MI+Dis组大鼠LVESD[(8.27±0.66)mm vs(5.82±0.54)mm]、LVEDD[(10.13±0.71)mm vs(7.97±0.55)mm]、心肌α-SMA、CollagenⅠ、CollagenⅢ相对表达量、血清TG、TC显著升高(P<0.05,P<0.01),LVEF、LVFS、心肌CPT-1β、PPARα的mRNA相对表达量显著降低(P<0.05)。结论昼夜节律紊乱可能通过抑制心肌脂肪酸β氧化,扰乱心脏能量代谢稳态导致脂质堆积,加重MI后心脏重构。Objective To investigate whether circadian rhythm disorders(CRD)exacerbate cardiac remodeling after MI and potential lipid metabolism-related mechanisms.Methods Eighteen healthy SPF-grade male SD rats were randomly divided into sham-operation(sham)group,MI group and CRD(MI+Dis)group,with 6 rats in each group.After 14 d of acclimatization,the MI and MI+Dis groups were established as MI models,and the MI+Dis group received 24 h continuous light for 7 d to establish a CRD model.Echocardiography was used to assess cardiac function,HE staining to observe MI-induced myocardial injury,Masson staining to measure myocardial collagen fiber expression,immunofluorescence assay to detect myocardial fibrosis markerα-SMA expression,RT-PCR to determine the mRNA levels of carnitine palmitoyltransferase 1β(CPT-1β),peroxisome proliferator-activated receptorα(PPARα),Collagen typeⅠand Collagen typeⅢ,and biochemical tests to measure the serum levels of triglyceride(TG)and total cholesterol(TC).Results The MI group had significantly larger LVESD and LVEDD and increased expression of myocardialα-SMA,CollagenⅠ,and CollagenⅢ,and reduced LVEF and LVFS when compared with the sham group(P<0.05,P<0.01).Obviously larger LVESD and LVEDD(8.27±0.66 mm vs 5.82±0.54 mm,10.13±0.71 mm vs 7.97±0.55 mm,P<0.05),increased expression levels of myocardialα-SMA,CollagenⅠand CollagenⅢ,and elevated serum TG and TC levels(P<0.05,P<0.01),and smaller LVEF and LVFS,and decreased myocardial CPT-1β,and PPARα(P<0.05)were observed in the MI+Dis group than the MI group.Conclusion CRD may lead to lipid accumulation and aggravate cardiac remodeling after MI by inhibiting myocardial fatty acidβoxidation and disturbing cardiac energy metabolism homeostasis.

关 键 词：心肌梗死 心肌 脂类代谢 心室重构 心房重构 生物钟紊乱 

分 类 号：R542.22[医药卫生—心血管疾病]