Effect of moxibustion combined with intraperitoneal injection of benazepril on endoplasmic reticulum stress-related protein phosphorylation in rats with chronic heart failure
Objective To observe the effect of moxibustion at"Xinshu"(BL15)and"Feishu"(BL13)com-bined with intraperitoneal injection of benazepril on cardiac function and phosphorylation of protein kinase R-like endo-plasmic reticulum kinase(PERK)and eukaryotic initiation factor 2α(eIF2α)proteins in myocardium of rats with chronic heart failure(CHF),so as to explore its potential mechanism underlying improvement of CHF.Methods A total of 42 male SD rats were randomly assigned to blank control(n=10),CHF model(n=7),medication(benazepril,n=8),moxibustion(n=8)and moxibustion+benazepril(n=9)groups,after cardiac ultrasound model identification and elimina-tion of the dead.The CHF model was established by intraperitoneal injection of doxorubicin hydrochloride(DOX),once every week for 6 weeks.Mild moxibustion was applied to bilateral BL15 and BL13 regions for 20 min,once daily for 3 weeks.The rats of the medication group and moxibustion+benazepril group(benazepril was given first,followed by moxibustion)received intraperitoneal injection of benazepril(0.86 mg/kg)solution once daily for 3 weeks.The cardiac ejection fraction(EF)and left ventricular fractional shortening(FS)were measured using echocardiography.Histo-pathological changes of the cardiac muscle tissue were observed under light microscope after hematoxylin-eosin(H.E.)staining.Serum contents of B-type brain natriuretic peptide(BNP)and angiotensin Ⅱ(Ang Ⅱ)were measured by enzyme-linked immunosorbent assay(ELISA).The expressions of phospho-PERK(p-PERK)and phospho-eIF2α(p-eIF2α)in the myocardium were detected by Western blot.Results Compared with the blank control group,the EF and FS of the left cardiac ventricle were significantly decreased(P<0.01),while the contents of serum BNP and Ang Ⅱ,and expression levels of p-PERK and p-elF2α significantly increased in the model group(P<0.01).In comparison with the model group,both the decreased EF and FS and the increased BNP and Ang Ⅱ contents as well as p-PERK and p-eIF2α expression levels were reversed by moxibustion,medication and moxibustion+benazepril(P<0.01).The effects of moxibustion+benazepril were markedly superior to those of simple moxibustion and simple medication in raising the levels of EF and FS rate and in down-regulating the contents of BNP,Ang Ⅱ,levels of p-PERK and p-eIF2α(P<0.01,P<0.05).Outcomes of H.E.staining showed irregular arrangement of cardiomyocytes,cell swelling,vacuole and inflam-matory infiltration in the model group,which was relatively milder in the 3 treatment groups.The effects of moxibustion+benazepril were superior to those of moxibustion or benazepril.Conclusion Moxibustion combined with Benazepril can improve the cardiac function in CHF rats,which may be related to its functions in down-regulating the expression levels of myocardial p-PERK and p-eIF2α to inhibit endoplasmic reticulum stress response.