| Objective:To investigate the improvement effect of ethanol extract of Taraxacum mongolicum Hand-Mazz(ETM)and its active ingredient dandelion polysaccharides(DP)on myocardial ischemia-reperfusion in rats,and to clarify the possible mechanism of regulation of Nrf2/HO-1/NLRP3 signaling pathway.Methods:84 healthy male SD rats(weight 250±20 g)were randomly divided into 7 groups with 12 rats in each group,namely the normal group(Cont),the model group(I/R),the trimetidine Tazidine group(TMZ),ETM high-dose group(ETMH),ETM low-dose group(ETML),DP high-dose group(DPH),DP low-dose group(DPL).The rat cardiac ischemia-reperfusion model was established by the Langendorff isolated heart perfusion device.The conditions of each group are as follows:(1)Control group:K-H normal buffer perfusion for 180 minutes;(2)model group:K-H normal buffer perfusion for 30 minutes 30 minutes later,the left anterior descending coronary artery was ligated for 30 minutes,and then perfused with K-H normal buffer for 120minutes;(3)Drug group:after 30 minutes of equilibrium perfusion with K-H normal buffer,the left anterior descending coronary artery was ligated for 30 minutes,and then 20 minutes after ischemia(10 minutes before loosening the ligature),the prepared drug was injected into normal K-H buffer for 30 minutes,and finally reperfused for 90 minutes;The powerlab physiological instrument was used to record and compare the hemodynamic changes among the groups,including left ventricular diastolic pressure(LVDP),left ventricular end-diastolic pressure(LVEDP),left ventricular systolic pressure(LVSP),maximal rate of the increase of left ventricular pressure(+dp/dt max),maximal rate of the decrease of left ventricular pressure(-dp/dt min);ELISA was used to detect the levels of LDH、c Tn-I、AST、ROS、MDA、SOD、GSH-PX、IL-6、TNF-αin myocardial tissue of each group;Evans Blue and TTC staining was used to detect the difference in myocardial infarction area among the groups;HE staining method was used to observe the morphological changes of myocardial tissue in each group;TUNEL staining was used to observe the difference in the apoptosis rate of each group;The protein expressions of Nrf2,HO-1,TXNIP,NLRP3 and cleaved-Caspase-1 in cardiomyocytes of each group were observed by Western Blot.Result:Compared with the Cont group,the LVDP,LVSP,+dp/dt max,-dp/dt min of the I/R group were significantly decreased,and the LVEDP was significantly increased(P<0.05)indicating that this experiment successfully established the myocardial ischemia-reperfusion in rats.Model.Compared with the I/R group,ETM and DP significantly improved left ventricular function,increased the levels of LVSP,+dp/dt max,-dp/dt min,and LVDP,and decreased the level of LVEDP.(P<0.05);decreased the release of LDH、c Tn-I、AST、ROS、MDA、IL-6、TNF-αcaused by myocardial ischemia-reperfusion,and enhanced the activities of SOD and GSH-PX(P<0.05);According to Evans Blue and TTC double staining observation,ETM and DP improved the structure and fiber integrity of rat cardiomyocytes.According to HE diagnosis and TUNEL staining observation,After treatment with the ETM and DP,the myocardial infarction area was significantly reduced and the apoptosis rate of cardiomyocytes was reduced(P<0.05).In addition,Western blotting showed that compared with the I/R group,ETM and DP significantly increased the protein expressions of Nrf2 and HO-1,while the protein expressions of TXNIP,NLRP3 and cleaved-Caspase-1 were significantly decreased(P<0.05).Conclusion:Ethanol extract of Taraxacum mongolicum Hand-Mazzand and dandelion polysaccharides protective effects on myocardial ischemia-reperfusion injury in rats,and the mechanism may be related to Nrf2/HO-1/NLRP3 signaling pathway and improving oxidative stress and inflammatory response induced by myocardial ischemia-reperfusion injury. |