Effect Of Adropin On The Expression Of Myocardial MMP-9and TIMP-1under Ischemia-reperfusion Injury In Mice

Objective: To observe the protective effect of reperfusion injury followingmyocardium ischemia with the posttreatment of different dose of the adropin．Toinvestigate that adropin may protect heart from MIRI with the involvement ofthe balance of matrix metalloproteinase (MMP-9) and tissue inhibitormetallproteinase-1(TIMP-1)．Methods: A mice model of myocardial ischemia-reperfusion was successfullyestablished．the left main coronary artery(LCA) of all mice was occluded for30minfollowed by reperfusion (R) for120min．Six groups of eight experimental mice，Group-I(Sham)mice， only threading without the coronary artery ligation，Group-II(Control) mice, without other interventions，Group-II（IPost）mice（ischemicpost-conditioning）were treated the same as Control and3cycles of10s R and10sI before R，Group-IV (AD-L)，Group-V(AD-M) and group-VI(AD-H) mice wereintravenously injected with adropin (0.1，0.2or0.4mg/kg) before5min of thereperfusion and then，120min later， creatine phosphokinase isoenzymes(CK-MB) and lactate dehydrogenase (LDH) were measured， size ofmyocardial infarct was assessed． Secondly， Four groups of thirty-twoexperimental mice were Sham，Control， Post and AD-M．MMP-9and TIMP-1were assessed2h after the reperfusion by RT-PCR and Western-blot respectively，zymography measures the enzymatic activity of MMP-9in serum．Results: After reperfusion (R) for120min，CK-MB and LDH levels were lower inSham mice than other groups(P<0.05)；comparing Control，Post、AD-M and AD-H were lower，CK-MB and LDH levels were lower in AD-M、AD-H mice than in AD-Lmice，but were no different from Post mice， there are no statistical significancebetween AD-L and Control mice．There is no area of necrosis in Sham mice，There isno statistical significance on AAR/LV in other groups．AN/AAR in Post、AD-M andAD-H is significantly lower than Control group(P<0.05)．AN/AAR was lower inAD-M、AD-H mice than inAD-L mice，yet was no different from Post mice，there isno statistical significance between AD-L and Control mice．The relative expression ofmRNA、protein and the enzymatic activity of MMP-9was lower in Sham mice thanControl，Post and AD-M mice，but the relative expression of TIMP-1mRNA、proteinwas higher．The relative expression of mRNA and protein and the enzymatic activityof MMP-9was lower in Post and AD-M mice than in Control mice，but the relativeexpression of TIMP-1mRNA and protein was higher in Post and AD-M mice than inControl mice(P<0.05)．There is no statistical significance on the above expression inAD-M mice than in Post mice．Conclusions:1、 The postconditioning of different dose of the adropin mayeffectively prevent MIRI，the dose is more，the protective effect is enhanced，namelydose-response relationship；2、Adropin may protect heart from MIRI with theinvolvement of attenuating the expression of MMP-9and enhancing the expressionof TIMP-1in mice．...