摘要
目的探讨分泌卷曲相关蛋白5(SFRP5)对缺血性心力衰竭(IHF)大鼠心肌细胞凋亡和心肌纤维化的影响及相关作用机制。方法40只SD雄性大鼠随机分为假手术组(Sham组)、模型组(IHF组)、SFRP5组、SFRP5+Wnt5a激动剂组(SFRP5+Foxy-5组),每组10只。采用超声心动图检测大鼠心功能指标;HE染色、Masson染色观察大鼠心肌病理学改变;TUNEL染色检测大鼠心肌细胞凋亡;免疫组织化学染色观察大鼠心肌组织纤连蛋白(Fn)、α-平滑肌肌动蛋白(α-SMA)、切割型半胱氨酸天冬氨酸蛋白水解酶-3(Cleaved Caspase-3)阳性表达情况;Western blot法检测大鼠心肌组织SFRP5蛋白、无翅型MMTV整合位点家族成员5a(Wnt5a)/c-Jun氨基末端激酶(JNK)信号通路蛋白表达。结果与Sham组比较,IHF组大鼠心功能指标左室舒张末期内径(LVEDd)、左室收缩末期内径(LVDs)、左室舒张末期容积(LVEDV)、左室收缩末期容积(LVESV)均增加,左室射血分数(LVEF)和左心室短轴缩短率(LVFS)均下降(P<0.05);心肌组织存在明显病理改变,心肌纤维化面积增加,心肌细胞凋亡率升高,心肌组织Fn、α-SMA和Cleaved Caspase-3阳性表达均增多(P<0.05);心肌组织SFRP5蛋白表达下降,Wnt5a蛋白表达、p-JNK/JNK比值均升高(P<0.05)。与IHF组相比,SFRP5组大鼠心功能指标和心肌损伤均得到改善,心肌纤维化面积减少,心肌细胞凋亡率降低,心肌组织Fn、α-SMA和Cleaved Caspase-3阳性表达均减少(P<0.05);心肌组织SFRP5蛋白表达升高,Wnt5a蛋白表达、p-JNK/JNK比值均下降(P<0.05)。与SFRP5组比较,SFRP5+Foxy-5组大鼠心功能指标异常,心肌损伤加重,心肌纤维化面积增加,心肌细胞凋亡率升高,心肌组织Fn、α-SMA和Cleaved Caspase-3阳性表达均增多(P<0.05);心肌组织Wnt5a蛋白表达、p-JNK/JNK比值均升高(P<0.05)。结论SFRP5可能通过抑制Wnt5a/JNK信号通路减轻心肌细胞凋亡和心肌纤维化,从而改善大鼠IHF。
AIM To investigate the effect of secreted frizzled-related protein 5(SFRP5)on myocardial apoptosis and myocardial fibrosis in rats with ischemic heart failure(IHF)and its mechanism.METHODS Forty SD male rats were randomly divided into sham operation group(Sham group),model group(IHF group),SFRP5 group,and SFRP5+Wnt5a agonist group(SFRP5+Foxy-5 group),with 10 rats in each group.The cardiac function indexes of rats were measured by echocardiography,the pathological changes of rat myocardium was observed by HE staining and Masson staining,and cardiomyocyte apoptosis in rats was detected by TUNEL staining.The positive expressions of fibronectin(Fn),α-smooth muscle actin(α-SMA)and cleaved cysteine aspartate proteolytic enzyme-3(Cleaved Caspase-3)were observed by immunohistochemistry and the expressions of SFRP5 protein and wingless-type MMTV integration site family member 5a(Wnt5a)/c-Jun N-terminal kinase(JNK)signaling pathway protein in rat myocardium were detected by Western blot.RESULTS Compared with those in the Sham group,left ventricle end diastolic dimension(LVEDd),left ventricular end systolic dimension(LVIDs),left ventricular end diastolic volume(LVEDV)and left ventricular end systolic volume(LVESV)of rats in IHF group were increased,while left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)were decreased(P<0.05).There were obvious pathological changes in myocardial tissue,the area of myocardial fibrosis and the rate of myocardial cell apoptosis were increased and the positive expressions of Fn,α-SMA and Cleaved Caspase-3 in myocardial tissue were also increased(P<0.05).The expressions of SFRP5 protein in myocardial tissue were decreased,while the expressions of Wnt5a protein and the ratio of p-JNK/JNK were increased(P<0.05).Compared with those in the IHF group,the indexes of cardiac function and myocardial injury of rats in SFRP5 group were improved,the area of myocardial fibrosis was reduced,the rate of myocardial cell apoptosis was decreased and the positive expressio
作者
刘军格
江正发
焦东生
刘莎
LIU Jun-ge;JIANG Zheng-fa;JIAO Dong-sheng;LIU Sha(The First Department of Cardiology,Shengjing Hospital of China Medical University,Shenyang 110004,Liaoning,China;Department of Cardiology,Ankang Central Hospital,Ankang 725000,Shaanxi,China)
出处
《心脏杂志》
CAS
2024年第4期379-386,共8页
Chinese Heart Journal
