Effect of poria cocos polysaccharides on myocardial ischemia-reperfusion injury in rats via regulating Nrf2/HO-1 signaling pathway
Objective It is to investigate the effect of poria cocos polysaccharides(PCP)on myocardial ischemia-reper-fusion injury(MIRI)in rats via regulating the nuclear factor E2 related factor 2(Nrf2)/heme oxygenase-1(HO-1)signa-ling pathway.Methods One hundred and thirty clean grade SD rats were randomly selected,in which 24 rats were selected as sham operation group,and the remaining 106 rats were used to establish MIRI models through blocking anterior descend-ing branch of left coronary artery for 30 min.96 successfully modeled rats were randomly divided into model group,PCP group,PCP+Nrf2 agonist group and PCP+Nrf2 inhibitor group,with 24 rats in each group.The PCP group was given PCP oral solution 3 mL/kg by gavage and normal saline by intraperitoneal injection,the PCP+Nrf2 agonist group was given PCP oral solution 3 mL/kg by gavage and TBHQ 20 mg/kg by intraperitoneal injection,the PCP+Nrf2 inhibitor group was given PCP oral solution 3 mL/kg by gavage and ML385 30 mg/kg by intraperitoneal injection,and the sham operation group and model group were given normal saline by gavage and intraperitoneal injection,all once daily,continuously treated for 4 weeks.The cardiac function[left ventricular ejection fraction(LVEF),maximum rate of increase/decrease of LV in-ternal pressure(+dp/dtmax,-dp/dtmax)]of the rats was examined by echocardiography,myocardial infarction was ob-served by TTC staining and the infarct volume was calculated,myocardial histopathologic morphology was observed by HE staining,myocardial apoptosis was observed by TUNEL staining,and serum levels of myocardial enzymes[lactate dehydro-genase(LDH),cardiac troponin I(cTnⅠ),myoglobin(Mb),creatine kinase isoenzyme(CK-MB)]and the contents of myocardial tissue oxidative stress indexes[malondialdehyde(MDA),superoxide dismutase(SOD),catalase(CAT)],inflammatory factors[interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)]were measured by ELISA,the protein expressions of Nrf2,HO-1,nuclear factor-κB p65(NF-κB p65),apoptosis related proteins(Caspase-3 and cleaved Caspase-3,Bcl-2,Bax)in myocardial tissue were detected by Western blot,and the mRNA ex-pression of Nrf2,HO-1 in myocardial tissue were detected by RT-PCR.Results Compared with the model group,the LVEF and+dp/dtmax,-dp/dtmax of rats in the PCP group and PCP+TBHQ group were significantly increased(all P＜0.05);the myocardial tissue infarct volume,cardiomyocyte apoptosis rate,and serum levels of LDH,cTnⅠ,Mb,and CK-MB were significantly reduced(all P＜0.05),and myocardial tissue pathological changes were significantly improved;the contents of MDA,IL-1β,IL-6,and TNF-α and the relative protein expressions of NF-κB p65,Bax,cleaved Caspase-3 in myocardial tissue,and Bax/Bcl-2,cleaved Caspase-3/Caspase-3 were significantly decreased(all P＜0.05),the contents of SOD,CAT and relative protein expressions of Nrf2,HO-1,Bcl-2 and relative mRNA expressions of Nrf2,HO-1 mRNA in myocardial tissues were significantly increased(all P＜0.05).The regulatory effects on the above indicators in the PCP+Nrf2 agonist group were significantly better than those in the PCP group(all P＜0.05),while the regulatory effects in the PCP group were significantly better than those in the PCP+Nrf2 inhibitor group(all P＜0.05).Conclusion Poria cocos polysaccharides could alleviate myocardial ischemia-reperfusion injury in rats and improve its cardiac function via inhibiting oxidative stress,inflammation and cell apoptosis,the mechanism may be related to the up-regulation of the Nrf2/HO-1 sig-naling pathway.
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