Effect Of Pretreatment With Pentamethylquercetin Against Cardiomyocytes Anoxia/Reoxygenation Injury

AIM： Pentamethyl-quercetin (PMQ), the quercetin methylation production, hasobvious pharmacokinetics feature and pharmacodynamics advantages can protectcardiomyocytes from anoxia/re-oxygenation injury. Primary neonatal SD ratcardiomyocytes were cultured and A/R injury model were established to explore theprotective effect of pretreatment with pentamethylquercetin on anoxia/reoxygenationinjury and mitochondrial function in rat cardiomyocytes.METHODS: Primary neonatal SD rat cardiomyocytes were cultured anddivided into eight groups randomly, every group repeated three times:(1) Controlgroup;(2) Control+DMSO group;(3) A/R group;(4) A/R+DMSO group;(5) DPCgroup;(6)10μmol/L PMQ+A/R group;(7)30μmol/L PMQ+A/R group;(8)100μmol/L PMQ+A/R group. After the treatment, MTT was used to analyzed cellsviability, the activity of LDH was determined by auto-biochemistry anaysator, cellapoptosis and mitochondrial membrane potential were detected by flow cytometry,opening of mitochondrial permeability transition pore (mPTP) was determined byCa2+-induced swelling of isolated cardiac mitochondria.RESULTS: After A/R, the cell viabilities were decreased, the content of MDAwas increased, the activities of SOD and GSH-Px were lower and LDH was higher,increased the level of ROS, the mitochondria membrane potential was markedlydecreased, and the apoptosis was higher than control group, and all indicators wereshowed A/R was successfully constructed (p<0.01); After DPC, the cell viabilitieswere increased, the content of MDA was decreased, the activities of SOD andGSH-Px were higher and LDH was lower, the mitochondria membrane potential wasmore stable, and the apoptosis was lower than A/R group, and all indicators wereshowed DPC was successfully constructed(p<0.01); Pretreated with different dose ofPMQ (10,30,100μmo/L) for24h could reduce LDH activity, increase cell viability,decrease cell apoptosis（P <0.05or P <0.01）in dose-dependent manner; Moreover,pretreated with30,100μmol/L PMQ for24h, mitochondrial membrane potentialcould be more stable（P <0.05or P <0.01）, and the opening of mPTP could be more lessened（P <0.05or P <0.01）.CONCLUSION: Pretreated with PMQ for24h could have Pharmacology delayprotectiont, the mechanism involved in inhibiting oxidative stress, stabilizingmitochondrial membrane potential, inhibiting mPTP opening, and reducing cellapoptosis.