Regulatory effect of soluble growth stimulator gene 2 protein on ventricular remodeling in rats with ischemic cardiomyopathy
Objective To explore the regulatory effect of soluble growth stimulator gene 2 protein(sST2)on ventricular remodeling in rats with ischemic cardiomyopathy(ICM).Methods The left coronary artery ligation method was used to establish the ICM rats model.Rats were randomly divided into model group(15 cases),empty vector group(15 cases)and drug group(15 cases).A sham operation group(15 cases)was set up.The empty vector group was subcutaneously injected with 1 mL of empty adenovirus.The drug group was subcutaneously injected with 1 mL adenovirus carrying sST2 vector to induce the overexpression of sST2.The model group and the sham operation group were subcutaneously injected with equal amount of normal saline.All rats fed normally for 1 week after continuous administration for 2 days.All rats were examined by echocardiography for ventricular remodeling indexes[left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDd),left ventricular end-systolic diameter(LVESd),interventricular septal thickness at diastole(IVSd)]one week after the last administration.The levels of serum sST2,myocardial injury markers[cardiac troponin I(cTnI),creatine kinase(CK),creatine kinase isoenzyme(CK-MB)]and inflammatory indicators[interleukin(IL)-33,IL-6,tumor necrosis factor α(TNF-α)]were detected.At the same time,the pathological changes of rat myocardial tissue and the degree of myocardial fibrosis were observed by hematoxylin-eosin(HE)staining and Masson staining.The expression of sST2 in myocardial tissue was detected by immunohistochemistry.Pearson correlation was used to analyze the correlation between sST2 expression level,inflammatory indicators and ventricular remodeling indicators.Results Compared with the sham operation group,the myocardial cells in the model group and empty vector group were arranged in disorder,with larger intercellular space and more obvious interstitial collagen deposition,and the myocardial cells in the drug group were arranged more irregularly,with larger intercellular space and more interstitial collagen deposition.LVEF and IL-33 in the model group,empty vector group,and drug group were lower than those in the sham operation group,and the above indexes in the drug group were lower than those in the model group and empty vector group(F=618.974,28.151;P<0.05).The levels of LVEDd,LVESd,IVSd,sST2,cTnI,CK,CK-MB,IL-6,and TNF-α in the model group,empty vector group,and drug group were higher than those in the sham operation group,and the above indexes in the drug group were higher than those in the model group and empty vector group(F=3.665,3.418,122.807,36.596,101.736,37.573,79.716,20.371,51.494;P<0.05).The expression level of sST2 in myocardial tissue of the model group,empty vector group,and drug group was higher than that of the sham operation group,and the sST2 expression level in the drug group was higher than that in the model group and empty vector group(F=122.843,P<0.05).The level of sST2 in serum and myocardial tissue of ICM rats was negatively correlated with ventricular remodeling index LVEF and inflammatory index IL-33(P<0.05),but positively correlated with LVEDd,LVESd,IVSd,IL-6,and TNF-α(P<0.05).Conclusion sST2 is associated with ventricular remodeling in ICM rats,and high expression of sST2 promotes the process of ventricular remodeling in rats.
RatIschemic cardiomyopathyVentricular remodelingSoluble growth stimulator gene 2 protein