| Objective:By observing the changes in myocardial pathology,myocardial water content,cardiac function and expression of myocardial tissue aquaporins?AQPs?via the intervention of Xinshuitong herbal water extract?XST?on rats with chronic heart failure?CHF?,to explore the effect mechanism of XST on CHF cardiac function.Method:Rat models of CHF were established by Doxorubicin,and rats were respectively administered with XST at a low dose of 4.9 g·kg-1,a medium dose of 9.8 g·kg-1,and a high dose of 19.6 g·kg-11 for 30 days.And the behavioral activity,diet and body weight change of rats were observed and recorded in each group.At four time points including before modeling,after modeling,as well as 15 days and 30 days after administration,the small animal ultrasound imaging system was used to detect cardiac function of rats in each group.Rats were executed after 30 days of administration,the concentration of serum myocardial troponin??cTn??,myocardial remodeling indexes,and myocardial water content were measured.The pathological microstructure of myocardial tissue was prepared and IHC,Western Blot and Q-PCR were used to detect cardiac AQP-1,4,7 mRNA and protein expression.Result:1.Ultrasound image of cardiac function:The ejection fraction?LVEF?of Adriamycin-induced model rat is less than or equal to 50%,which confirms that the CHF model was successfully constructed.The thickness of left ventricular systolic anterior wall?IVSs?,thickness of diastasis anterior wall?IVSd?,thickness of systolic posterior wall?LVPWs?,thickness of diastasis posterior wall?LVPWd?,LVEF and left ventricular fractional shortening?LVFS?were significantly reduced?P<0.05?,the left ventricular end-systolic dimension?LVIDs?,left ventricular end-diastolic dimension?LVIDd?were significantly increased?P<0.01?compared with the normal group.During administration,LVIDs of the XST low-dose group were reduced?P<0.05?,and LVPWd,LVEF,LVFS of low-dose XST group were increased?P<0.05?compared with the model group.The IVSs,IVSd,LVPWs,LVPWd,LVEF,LVFS were increased?P<0.05?,and LVIDs,LVIDd were decreased?P<0.01?in the XST medium-dose and high-dose group compared with the model group.The cardiac function of rats in the CHF model group was progressively deteriorated during the experiment.Compared within the same group,the cardiac function of the XST medium-dose and high-dose group was improved more obviously after 30 days of administration than that after 15 days of administration,and the cardiac function of the high-dose group was improved more significantly.It is suggested that the drug can improve the heart function of heart failure.2.Observation of behavioral signs:A poor mental state,poor mobility,a gradual decrease in diet,weight loss,and obvious symptoms of heart failure such as severe ascites and diarrhea were appeard in the CHF model group.Compared with the model group,diet and weight of rat increased?P<0.05?,behavioral signs are good and mortality is relatively low in the XST medium-dose and high-dose group.It is indicated that the hearb water extract can improve the quality of life,prolong life in rats with heart failure.3.Concentration of serum cTN?:The concentration of rat serum cTN?in CHF model group increased significantly?P<0.01?compared with the normal group.cTN?concentration of XST low-dose group decreased?P<0.05?,and the concentration of high-dose group decreased significantly?P<0.01?compared with model group.The concentration in the high-dose group was the lowest,which indicated that the drug has a good protective effect on cardiomyocytes.4.Cardiac mass index and myocardial water content:The diameter of myocardial cell in left ventricular free wall,cardiac mass index,left ventricular mass index,and myocardial water content in the CHF model group significantly increased?P<0.01?compared with the normal group.The myocardial fibrous diameter,cardiac mass indexes,and myocardial water content of the rats in the XST medium-dose and high-dose groups were reduced?P<0.05?compared with the model group,and the best improvement of all data is in the high-dose group.It is suggested that XST can not only improve the myocardial remodeling of heart failure,but also improve myocardial edema of heart failure.5.Myocardial tissue pathology:The myocardial fibers of normal group arranged neatly without any pathological changes in the cells.In the model group,myocardial fibers were hypertrophic and arranged in a wave shap.Degeneration,necrosis,and interstitial widening were appeared in some myocardial cells.In the XST low-dose group,the hypertrophic degree of cardiomyocytes was slightly lower than that in the model group,the arrangement of myocardial fibers was disordered,some myocardial fibers were broken and the myocardial interstitial was widened.In the XST medium-dose and high-dose groups,the permutation density of myocardial fibers was denser than the model group,the hypertrophic degree,degeneration,and necrosis of cardiomyocytes of the XST medium-dose and high-dose group were lower than the model group.The degree of improvement in cardiomyocytes of the high-dose group was particularly obvious.It is showed that the drug can improve the myocardial remodeling of heart failure and protect myocardial cells.6.Detection of AQP-1,4,7mRNA expression by Q-PCR:The expression level of myocardial AQP-1,4,7 mRNA of rats in the CHF model group was significantly increased?P<0.01?.The expression level of AQP1 mRNA in the low-dose XST group was reduced?P<0.05?,the expression level of AQP-1,4,7 mRNA in the medium-dose group and AQP-1,4mRNA in the high-dose group were significantly reduced?P<0.01?compared with the model group.Among them,the expression level of AQP1 mRNA in the high-dose XST group was lower than that in the middle-dose group,while the level of AQP-4,7 mRNA in the middle-dose group was lower than that in the high-dose group.It is suggested that XST has different degrees of regulation on AQP-1,4,7 mRNA in the heart of rats with heart failure,and the medium-dose group has a stronger effect on AQP-4,7 mRNA.7.Immunohistochemical detection of AQP-1,4,7 protein expression:AQP-1,4,7 are maily located in vascular endothelial cells and cardiomyocytes of heart in rats,the expression level of which in the CHF model group was significantly increased?P<0.01?compared with the normal group.The expression level of AQP1 in the XST low-dose group decreased?P<0.05?,the expression level of AQP-1,4,7 protein in the middle-dose group decreased significantly?P<0.01?,and the expression level of AQP-1,4 in the high-dose group decreased significantly?P<0.01?compared with the model group.AQP1 expression was lowest in the high-dose XST group,and AQP-4,7 was lowest in the medium-dose group compared among the three dose groups.It is suggested that the effect of different doses or the same dose of XST on myocardial AQPs is different.8.Detection of AQP-1,4,7 protein expression by Western blot:The expression level of myocardial AQP-1,4,7 protein of rats in the CHF model group was increased?P<0.05?compared with the normal group.The expression level of AQP1 in the XST low-dose group was reduced significantly?P<0.01?,The expression level of AQP-1,4,7 protein in the middle-dose group was reduced significantly?P<0.01?,and the decrease of AQP-1,4 in the high-dose group was obviously?P<0.01?compared with the model group.The most decrease of AQP1 was in the XST high-dose group,while the most decrease of AQP-4,7 was in the middle-dose group.Conclusion:Xinshuitong herbal water extract can improve the structure of cardiomyocytes,myocardial edema,cardiac function,the quality of life and survival rate of rats with chronic heart failure,which may be related to regulation of the overexpression of cardiac AQP-1,4,7 mRNA and protein. |
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