Sofren Attenuates Myocardial Ischemia-reperfusion Injury Aggravated By PM_2.5Exposure In Rats Via Inhibiting Apoptosis Induced By Endoplasmic Reticulum Stress

Objective:To investigate the effect of PM_2.5 exposure on myocardial ischemia-reperfusion injury（MIRI）in rats and the protective effect and mechanism of sofren injection from myocardial apoptosis induced by endoplasmic reticulum stress.Methods:Particulate matter of air was collected and suspended in normal saline.48 SPF Sprague-Dawley male rats were divided into 4 groups according randomized block design:①Sham-operated group（n=12）:left anterior descending coronary artery was only threaded;②I/R group（n=12）:left anterior descending coronary artery was ligated for 30min and then reperfused;③PM+ I/R group（n=12）:PM_2.5（10mg/（kg · time）,diluted to 0.4 mL by normal saline,once every 48 h for 3 times）was dropped into trachea slowly,I/R was performed 24 h after the last infusion;④DZ group:after 0.5 h of PM_2.5 tracheal instillation and I/R,sofren injection（3mL/（kg · d））was injected by intraperitoneal injection for 3 times.Sham-operated group,I/R group were gave the same volume of PM_2.5 normal saline through intratracheal instillation before surgery,once every 48 h for 3times.Sham-operated group,I/R group and PM_2.5+I/R group were injected the same volume of normal saline for 3 d.At the end of the experiment,echocardiography was detected after anesthesia.The expression of endoplasmic reticulum stress related protein GRP78,CHOP were detected by western blot and qRT-PCR;western blot was also used to detect whether XBP1 was spliced or not;TUNEL was used to detect the rate of cardiomyocyte apoptosis.Results:Compared with I/R group,left ventricular ejection fraction（LVEF）and left ventricular fractional shortening（LVFS）in PM+I/R group decreased significantly,myocardial apoptosis rate increased significantly,GRP78,CHOP transcription,protein levels,XBP1s/XBP1u increased significantly（P<0.01）.Compared with PM+I/R treatment group,LVEF and LVFS of DZ group increased significantly,myocardial apoptosis rate decreased significantly,GRP78,CHOP expression in transcription and protein levels decreased significantly（P<0.01）,XBPls/XBPlu decreased significantly（P<0.05）.Conclusion:Exposure to PM_2.5 can aggravate MIRI.Treatment of sofren injection attenuates MIRI after PM_2.5 exposure in improvement of cardiac function and decreased apoptosis.The mechanism may be related to inhibition of apoptosis induced by endoplasmic reticulum stress.