浅低温对心肌缺血-再灌注损伤合并脓毒症大鼠模型的心肌保护作用

目的:探究浅低温对心肌缺血-再灌注损伤合并脓毒症大鼠模型的心肌保护作用.方法:共15只SD大鼠随机分为心肌缺血-再灌注损伤合并脓毒症浅低温(MHT)组、心肌缺血-再灌注损伤合并脓毒症常温(NT)组和假手术常温组作为对照组.大鼠心肌缺血后再灌注同时给予内毒素,然后MHT组将大鼠置于冰床降温,15 min内达(33.0±0...

Cardioprotective Effect of Mild Hypothermia in Rats With Myocardial Ischemia-reperfusion Injury Combining Sepsis

Objectives:To investigate the cardioprotective effect of mild hypothermia in rats with myocardial ischemia-reperfusion injury(MIRI)and sepsis.Methods:A total of 15 SD rats were randomly allocated into three groups:MIRI combining sepsis in mild hypothermia(MHT,[33.0±0.5]℃)group,MIRI combining sepsis in normothermia(NT,[37.0±0.5]℃)group and sham in NT group(control).Rats in MIRI combining sepsis group received lipopolysaccharide(LPS,15 mg/kg,i.p.)at the beginning of reperfusion.After LPS injection,rats in MHT group were place on an ice bed.Target temperatures(33.0±0.5)℃reached within 15 min and maintained for 2 h.Cardiac function,lactate dehydrogenase(LDH),creatine kinase(CK)-MB,myocardial infarct size,pathological change,nicotinamide adenine dinucleotide phosphate oxidase(NOX2),cysteinyl aspartate specific protease(caspase)-3 and tumor necrosis factor(TNF)-αwere assessed at 2 h of target temperature maintenance.Results:Blood sample and heart were obtained at the end of 2 h temperature maintenance.In MHT group,heart rate was lower than NT group([396.63±39.93]bpm vs.[457.74±32.77]bpm,P<0.05);left ventricular maximal systolic pressure at 2 h of reperfusion was significantly higher than NT group([129.14±34.05]mmHg vs.[85.63±14.74]mmHg,1 mmHg=0.133 kPa,P<0.05);+max dp/dt,LVEDp and-min dp/dt in MHT group at 2 h of reperfusion also tended to be higher than NT group(P>0.05).LDH in MHT group was significantly reduced compared to NT group([1153.61±127.85]U/L vs.[2213.34±599.60]U/L,P<0.05).CK-MB showed similar results in MHT group as compared to NT group([1103.22±114.75]U/L vs.[1731.33±688.05]U/L,P<0.05).Hemoxylin-eosin(HE)staining presented less inflammatory infiltration,necrosis and blood congestion in myocardium of MHT group compared with NT group.Myocardial infarct size in MHT group was significantly lower than in NT group([11.23±2.82]%vs.[19.25±4.45]%,P<0.05).Moreover,Western blot evidenced a trend of downregulated expression of NOX2 in MHT group as compared with NT group(P>0.05).Expression of caspase-3 in MHT group was significantly lower than in NT([1.06±0.34]%vs.[3.27±0.67]%,P<0.05).In addition,TNF-αexpression was also significantly downregulated in MHT group than in NT([12.23±3.31]%vs.[31.14±1.69]%,P<0.05).Conclusions:Mild hypothermia exerts cardioprotective effect in MIRI combining sepsis rat model by improving myocardial dysfunction,decreasing infarct size,attenuating myocardial injury,inflammation,oxidative stress and apoptosis.