Diminished AdipoR1/Caveolin3Interaction Mediates Reduced Cardioprotective Actions Of Adiponectin In Type2Diabetes Mellitus

Objective Adiponectin (APN) system malfunction is causatively related to increasedcardiovascular morbidity/mortality in diabetic patients. The aim of the current study was toinvestigate molecular mechanisms responsible for APN transmembrane signaling andcardioprotection.Methods Select C57BL/6J male mice (6-8weeks), weighing30±12g, randomlydivided into five groups (n=10). Normal control group only coronary threading withoutligation; Ischemia-reperfusion (MI/R) group (MI/R+Scramble SiRNA) and Cav3SiRNAtreatment group (MI/R+Cav3SiRNA) prior to surgery for48hours to medicines, ligationof the left anterior descending artery for ischemia (MI) and30min later loosen the ligaturereperfusion; APN treatment group (MI/R+Scramble SiRNA+gAPN) injection ScrambleSiRNA to myocardial48hours later,at MI20min, given gAPN intraperitoneal injection; Cav3SiRNA and APN treatment group (MI/R+Cav3SiRNA+gAPN) timing of administration,dose and surgical like the previous. Ultrasound echocardiography in detecting heart function,Even’s blue-the TTC double staining method detects myocardial infarction area, andCaspase-3apoptotic protease activity detection, Western blot detects AMPK, the ACC eNOS,Akt and iNOS and gp91.Results①Compared with the control group, MI/R heart function significantlyreduce and the aggravation of myocardial injury,the difference was significant statistically (P<0.05)②Without Cav-3mice to give gAPN treatment, causing MI/R injury, improveLVEF%and significantly reduced myocardial injury; prompted adiponectin can significantly improve the ischemia-reperfusion myocardial damage.③SiRNA Cav-3mice(Cav3-\-) to give gAPN treatment, MI/R injury in mice heart function (LVEF%) rise andmyocardial injury not as good as WT treatment group. Tip may be due to the interference ofthe Cav-3, leading to adiponectin resistance, thus reducing the protective effect of adiponectinin ischemic heart disease. Compared with WT, Cav3-\-group showed a relatively steadyincrease myocardial ischemia-reperfusion injury, including increase myocardial infarct sizeand cardiac function lower (P <0.01). Experimental study found that WT group APNtreatment has a strong role in myocardial protection while Cav3-\-mice display myocardialprotective effect is to reduce or even completely disappear after MI/R ’s. The experimentalresults of this study Westen blot Cav3-\-mouse and the WT mice myocardium express weresignificantly higher while giving gAPN treatment and AMPK, ACC, eNOS,iNOS, gp91isactivated.Tip AdipoR1/Cav3interaction through AMPK pathway as well as some non-AMPKpathway in adiponectin myocardial protection also play a key role.Conclusions Naloxone is effective in improving ischemia-reperfusion hemodynamiceffects in rats and reduces the incidence of arrhythmia, reduces myocardial tissue necrosis,reduces infarct size, reduces apoptosis index. Naloxone has protective effect on myocardialischemia-reperfusion.