Discussion on the mechanism of Linggui Qihua Fomular in the treatment of heart failure with preserved ejection fraction based on PI3K/Akt/GSK3β signaling pathway
Objective To explore the mechanism of Linggui Qihua Formula(LGQHF)for the treatment of heart failure with preserved ejection fraction(HFpEF)based on phosphoinositide-3 kinase(PI3K)/protein kinase B(Akt)/glycogen synthase kinase-3beta(GSK3β)signaling pathway.Methods Fifty spontaneously hypertensive rats(SHR)and 10 Wistar-Kyoto(WKY)rats were randomly divided into the WKY group,the SHR group,the sakubutrazol valsartan sodium group,the HFpEF group,and the LGQHF low-dose group and the LGQHF high-dose group.with 10 rats in each group.The model was established by feeding high salt,high fat and high sugar diet combined with intraperitoneal injection of streptozotocin solution(STZ).Saline was given to the SHR and the WKY groups after modeling,and the remaining groups were gavaged with the corresponding drugs for 6 weeks.Ultrasound detection was performed before and after drug administration to detect the left ventricular anterior wall thickness(LVAWD),left ventricular posterior wall thickness(LVPWD),left ventricular end diastolic internal diameter(LVEDD),left atrial diameter(LAD)and right atrial diameter(RAD),left ventricular early diastolic filling peak velocity(E),atrial systolic left ventricular filling peak velocity(A),early diastolic lateral mitral annulus velocity(e'),E/A,E/e',isovolumic relaxation time(IVRT)and left ventricular ejection fraction(LVEF).ELISA to detect atrial natriuretic peptide(ANP)and B-type natriuretic peptide(BNP).The structural and morphological changes of the myocardial tissues of the rat were observed by HE and Masson staining.Western blot to detect the expression of related proteins of PI3K/Akt/GSK3β signaling pathway(Akt,PI3K,p-PI3K,GSK3β,p-GSK3β).Results Compared with the HFpEF group,LGQHF improved cardiac structure and function in HFpEF rats:(1)The results of Cardiac ultrasound showed that rats in the sakubutrazol valsartan sodium group,the LGQHF low-dose group and LGQHF high-dose group showed significant decreases in the values of LVEDD,LVAWD,LVPWD,LAD,RAD,E/A,E/e',and IVRT(P<0.01),and significant increases in the value of e'(P<0.01).The value of A was increased in the LGQHF high-dose group(P<0.05).There was no significant difference in LVEF and E(P>0.05).(2)Pathological results showed that the ventricular cavities of the rats in the administered group were smaller,the ventricular walls were thinner,and the fibers were less fractured and more tightly arranged.(3)The results of ELISA showed that the levels of BNP and ANP levels were decreased in the the sakubutrazol valsartan sodium group,the LGQHF low-dose group and LGQHF high-dose group(P<0.01).(4)The results of western blot showed that Akt,p-Akt and GSK3β protein expression was up-regulated in the Entresto group(P<0.05 or P<0.01).p-Akt and GSK3β protein expression was up-regulated in the LGQHF low-dose group(P<0.05 or P<0.01).And p-Akt protein expression was up-regulated in the LGQHF high-dose group(P<0.05).Conclusion The treatment of HFpEF rats with LGQHF was characterized by inhibition of cardiac remodeling,improvement of cardiac diastolic function,and reduction of serum BNP and ANP,which may be achieved through the PI3K/Akt/GSK3β signaling pathway.
heart failure with preserved ejection fractionLinggui Qihua Formulasignaling pathwaycardiac remodelingdiastolic function
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