Effect And Mechanism Of Kanli Granule On Pressure Overload Myocardial Hypertrophy

Objective: Taking the rat model of myocardial hypertrophy caused by pressure overload caused by abdominal aortic coarctation as the research object,the changes of pathological myocardial hypertrophy in rats with pressure overload were observed.The aim of our research was to confirmed that the myocardial hypertrophy of rats caused by pressure overload showed maladaptive myocardial hypertrophy,while after intervention with Kanli Granule,rats with myocardial hypertrophy induced by pressure overload showed adaptive hypertrophy,from the aspects of myocardial tissue structure,function and fetal gene expression.The mechanism of Kanli Granule prolonging compensatory period of myocardial hypertrophy was preliminarily discussed from the relationship between IGF-1/PI3Ka/Akt pathway and adaptive myocardial hypertrophy,and the mechanism of Kanli Granule was further elucidated.Methods: Seventy rats with pressure overload myocardial hypertrophy induced by abdominal aortic coarctation were randomly divided into model group,perindopril group and Kanli granule low,medium and high dose group.There were 14 rats in sham operation group,totally 6 groups.The sham operation group and model group were fed with double steaming water,and the drug group was fed with corresponding drugs for32 weeks.After anesthesia,LVDd,LVSd,LVSd,LVPWd and LVEF were measured by echocardiography,SAP,DAP,LVSP,LVDP,LVEDP,+LVdp/dt were measured by hemodynamics,and the changes of cardiac function and body shape were observed.The animals were sacrificed,the hearts were separated,and the cardiac gross anatomical changes were observed.HE staining and immunohistochemical collagen I/III staining were performed on the cardiac tissues.The morphological changes of myocardium and interstitial tissues were observed under light microscopy,and the ultrastructural changes of myocardial cells were observed by transmission electron microscopy.Western Blot and q-PCR were used to detect the expression of ANP,BNP,?/?MHC and the gene and protein levels of IGF-1/PI3Ka/Akt pathway in embryonic myocardium.Results:(1)Cardiac ultrasonography: Compared with sham-operated group,LVSd and LVPWd in model group increased significantly,while LVEF decreased significantly(P<0.05);Compared with model group,LVEF in low-dose group and medium-dose group increased significantly(P<0.05),LVWd in low-dose group(P<0.05),middle-dose group(P<0.05),high-dose group(P<0.01)increased significantly;and LVWd in perindopril group increased significantly.Compared with the Li group,the LVPWd in the Kanli granule high dose group increased significantly(P<0.01).(2)Hemodynamic indicators: Compared with sham-operated group,SAP and LVEDP in model group increased significantly,while + LVdp/dt decreased significantly(P<0.05);compared with model group,the + LVdp/dt in low-dose group,high-dose group and perindopril group increased significantly(P<0.01).(3)Cardiac gross anatomical changes: CW,LVW,CW/BW,LVW/BW data in model group were significantly higher than those in sham-operated group(P<0.01);compared with model group,CW/BW and LVW/BW in perindopril group were significantly lower(P<0.01)and lower(P<0.05).In the sham-operated group,the whole heart was small and the wall was thin;in the model group,the whole heart was large and the wall was thick;in the perindopril group,the whole heart was not significantly enlarged,and the wall was thin.In the low,middle and high dose groups,the ventricular wall was hypertrophic to varying degrees,and the ventricular cavity was not enlarged.(4)Immunohistochemical staining of collagen type I/III: collagen type I and III increased significantly in model group(P<0.01),collagen I/III ratio decreased significantly(P<0.05);compared with model group,collagen type III decreased significantly in low dose group(P<0.01),medium dose group(P<0.01),high dose group(P<0.05),perindopril group(P<0.01);and perindopril group(P<0.01).Compared with the control group,collagen III in the high dose group of Kanli Granule was significantly higher(P<0.05).(5)Gene index of myocardial embryo: Compared with sham operation group,BNP in model group increased significantly(P<0.05),and alpha MHC/beta MHC decreased significantly(P<0.01);compared with model group,the expression of alpha MHC/beta MHC in medium dose group of Kanli Granule increased significantly(P<0.01).(6)The expression of genes and proteins in the IGF-1/PI3Ka/Akt pathway: Compared with the model group,Kanli granule could increase the expression of genes and proteins in the IGF-1/PI3Ka/Akt pathway.Conclusion: In this study,we found that rats with pressure overload myocardial hypertrophy exhibited maladaptive myocardial hypertrophy.After intervention withKanli Granule,myocardium showed adaptive myocardial hypertrophy,which was characterized by persistent hypertrophy,but the cardiac function remained at a better level.The morphology of myocardial cells was intact,the proportion of collagen was coordinated,and the re-expression of fetal genes was inhibited.Kanli Granule can inhibit maladaptive myocardial hypertrophy and prolong the compensatory period of myocardial hypertrophy through IGF-1/PI3Ka/Akt pathway.