| Objective To investigate the protective effect of preconditioningwith Resveratrol on myocardial ischemia reperfusion in rats and theinhibition of apoptotic effect during myocardium ischemia reperfusion aswell as the relevance of PI3K-Akt signaling pathway.To expound themechanism of action of resveratrol from the signaling pathwany,supplyingnew theory support for its clinical practice.Providing clue for traditionChinese medical science treating.Looking for the drones of resveratrol inits action,to providing clue for new drug researching.Methods50healthy male SD rats were randomly divided into5groups (n=10):sham-operated group (SH group); ischemia-reperfusion group (IR group);Resveratrol preconditioning group (Res group); Res preconditioning+Wom group (Res+Wom group); ischemia-reperfusion+Wom group(IR+Wom group). The model of acute myocardium ischemia reperfusioninjury was performed by45min occlusion of left descending coronaryartery followed by120min reperfusion in open-chest rats.(1) SH Group: a non-ischemic control group of sham-operated rats, normal saline wasadministered i.v1ml separately at the threading time and the forty-sixthminute from the sublingual vein;(2) IR Groups: normal saline wasadministered i.v1ml1min before the ligation and reperftion,45min ofmyocardial ischaemia followed by120min reperfusion.；(3) Res Group:Resveratrol was administered i.v (20mg/kg)1min before ligation andreperfusion through the sublingual vein, the other with the same of IRgroup.；(4) Res+Wom group: the selective PI3K inhibitor Wom and Res (20mg/kg) were administered i.v1min before ligation ang reperfusion fromthe sublingual vein, the other with the same of Res group.；(5) IR+WomGroup:Wom was administered i.v1min before ligation and reperfusion, theother with the same of IR group. The left ventricular systolic pressure(LVSP), left ventricular end-diastolic pressure (LVEDP), maximum rates ofleft ventricular pressure development and decay (±dp/dtmax) were recordedat before ischemia,30min ischemia and reperfusion60,90,120min；Arterial serum nitric oxide (NO) and nitric oxide synthase (NOS) weredetermined by chemical colorimetry；The expressions of Bcl-2and Baxsignaling proteins were determined by immunohistochemistry. Myocardialapoptosis was determined byterminal deoxynucleotidyl transfease-mediateddUTP nick end labeling(TUNEL) methods．The myocardial T-Akt andp-Akt signaling proteins expressions were determined by Western blotanalysis. Results1Hemodynamic effects of ResveratrolThe hemodynamic was no significant difference before ischemia ineach group (P>0.05). Compared with group SH, LVSP and+dp/dtmaxweredecreased progressively, LVEDP and-dp/dtmaxwere progressivelyincreased at each time compared with other groups (P<0.05). In Resveretrolpreconditioning group, the LVSP and+dp/dtmaxwere increased, LVEDPand-dp/dtmaxwere lowered (P <0.05), Res+Wom group and IR+Womgroup were no significantiy differences (P>0.05) as compared with those ingroup IR. Compared with group Res, the LVSP and+dp/dtmaxwere loweredsignificantly,LVEDP and-dp/dtmaxwere significantly higher in groupsRes+Wom and IR+Wom (P<0.05).2The NO and NOS levels of Resveratrol in preconditioningCompared with IR group, the NO and NOS levels were significantlyincreased in group Res (P<0.05), Res+Wom group and IR+Wom groupwere no significantly differences (P>0.05). The NO and NOS levels weresignificantly lowered in groups Res+Wom and IR+Wom as comparedwith those in group Res (P<0.05).3The experesions of Bcl-2and Bax in Resveratrol preconditioningCompared with IR group, the level of Bcl-2was significantlyincreased in group Res (P<0.05), Bax/Bcl-2was lower than group IR;whenWom was used,controlled with Res group,the level of Bcl-2was significantly lowered (P<0.05), Bax/Bcl-2was increased in Res group.Thelevels of Bcl-2and Bax/Bcl-2in group Res+Wom,group IR and groupIR+Wom group,there were no significantly differences (P>0.05).4Antiapoptoticeffect of Resveratrol preconditioning inCardiomyocytesCompared with SH group, the other four groups increasedcardiomyocytes apoptosis significantly (P<0.05). Compared with group IR,Res group reduced cardiomyocytes apoptosis (P<0.05), Res+Wom groupand IR+Wom group cell apoptosis were no significantly differences. Ingroups Res+Wom and IR+Wom, the cardiomyocytes apoptosis wereincreased significantly as compared with group Res (P <0.05).5Akt phosphorylation induced by resveratrol preconditioningAccording the experiment results,there were no significantlydifferences in T-Akt.Compared with SH group, the expression ofmyocardial p-Akt protein was increased in groups IR and Res (P<0.05). InRes group, the expression of myocardial p-Akt protein was increasedsignificantly as compared with group IR (P<0.05). Compared with Resgroup, the expression of myocardial p-Akt protein level was decreaseed ingroups Res+Wom and IR+Wom group (P<0.05). ConclusionResveratrol significantly attenuated myocardial ischemia-reperfusioninjury. These cardioprotective effects are attributed mainly to antiapoptoticeffects of Resveratrol via a PI3K/Akt signaling pathway. |
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