氯高铁血红素预先给药对感染性休克大鼠心肌损伤的影响

Effects of heroin pretreatment on myocardial injury of rats with septic shock

目的探讨氯高铁血红素预先给药对感染性休克大鼠心肌损伤的影响。方法健康清洁级SD大鼠20只,雌雄不拘,2～2.5月龄,体重160～185g,随机分为2组（n=10）,感染性休克组（S组）单次腹腔注射0.9%NaCl溶液1ml,氯高铁血红素预先给药组（H组）单次腹腔注射氯高铁血红素100mg/kg（1m1）。2组均于给药后24h采用静脉注射脂多糖（LPS）10mg/kg（0.5ml）制备感染性休克模型。于静脉注射LPS前、注射LPS后30、60和90min时,记录左心室收缩压（LVSP）和左心室压力最大上升和下降速率（±dp/dtmax）。于静脉注射LPS后6h经颈总动脉采集血标本,放血处死大鼠,取左心室心肌组织,测定血浆乳酸脱氢酶（LDH）和肌酸激酶（CK）活性、全血一氧化碳血红蛋白（COHb）浓度及心肌血红素氧合酶（HO）-1 mRNA、HO-2 mRNA及其蛋白的表达。结果与S组比较,H组静脉注射LPS前LVSP和±dp/dtmax差异无统计学意义（P〉0.05）;注射LPS后各时点LVSP和±dp/dtmax升高,血浆LDH和CK活性降低,全血COHb浓度升高,心肌HO-1 mRNA及其蛋白表达上调（P〈0.05）,HO-2 mRNA及其蛋白表达水平差异无统计学意义（P〉0.05）。结论氯高铁血红素100mg/kg预先给药可通过诱导HO-1生成减轻感染性休克大鼠心肌损伤。

Objective To investigate the effects of hemin pretreatment on myocardial injury of rats with septic shock.Methods Twenty healthy SD rats of both sexes aged 2.0-2.5 months weighing 160-185 g were randomly divided into 2 groups （ n = 10 each） ： group Ⅰ septic shock （S） and group Ⅱ heroin pretreatment （ H）. Septic shock was induced by intravenous injection of LPS 10 mg/kg （in 0.5 ml）. Hemin pretreatment group received heroin 100 mg/kg （in 1 ml） intraperitoneally 24 h before induction of septic shock. Left ventricular systolic pressure （LVSP） and ＋ dp/dtmax were continuously monitored and recorded before LPS injection （baseline） and at 30, 60 and 90 min after septic shock had developed. Plasma LDH and CK activities, blood COHb concentration and myocardial HO-1 mRNA and protein expression and HO-2 mRNA and protein expression were determined at 6 h after LPS injection. Results The LVSP, ± dp/dtmax and blood COHb concentration were significantly higher while the plasma LDH and CK activities were significantly lower in group H than in group S after shock had developed. The myocardial HO-1 mRNA and protein expression was significantly higher in hemin pretreatment group （H） than in group S, but there was no significant difference in myocardial HO-2 mRNA and protein expression between the 2 groups. Conclusion Hemin pretreatment can reduce myocardial injury during septic shock by increasing myocardial HO-1 protein expression.