血红素加氧酶-1在脓毒症大鼠炎性反应中的作用

Role of heme oxygenase-1 in inflammatory responses in septic rats

目的评价血红素加氧酶-1（HO-1）在脓毒症大鼠炎性反应中的作用。方法雄性Wistar大鼠72只，10．14周龄，体重250—300g，以盲肠结扎穿孔法（CLP）建立脓毒症模型。采用随机数字表法，将大鼠随机分为4组（n=18）：对照组（C组）、脓毒症组（CLP组）、钴原卟啉Ⅸ组（Co组）及锌原卟啉Ⅸ组（Zn组）。于术后6、12、24h（T1-3）时随机取6只大鼠采集血样，采用ELISA法检测血清孙Ba、IL-6和高迁移率族蛋白B1（HMGB1）的浓度。于L时采集血样后取肺组织，采用RT-PCR法测定肺组织HMGB1mRNA表达。另取40只相同条件的Wistar大鼠，按照上述方法分组，绘制生存曲线。结果与C组比较，CLP组、co组和zn组血清TNF-α、IL-6和HMGB1浓度升高，肺组织HMGB1mRNA表达上调，生存率降低（P〈0．05）。与CLP组比较，Co组血清TNF-α、IL-6和HMGB1浓度降低，肺组织HMGB1mRNA表达下调，生存率升高（P〈0．05），Zn组上述指标差异无统计学意义（P〉O．05）。结论诱导HO-1表达有助于减轻脓毒症大鼠炎性反应。

Objective To evaluate the role of heine oxygenase-1 （HO-1） in inflammatory responses in septic rats.Methods Seventy-two male Wistar rats, aged 10-14 weeks, weighing 250-300 g, were used in this study. The animals were anesthetized with intraperitoneal 2% pentobarbital sodium 50 mg/kg. Sepsis was induced by cecal ligation and puncture （CLP）. The animals were randomly divided into 4 groups （ n = 18 each） . control group （C group）, CLP group, HO-1 inducer cobalt protoporphyrin IX （CoPP~） group （Co group） and HO-1 in- hibitor zinc protoporphyrin IX （ZnPPIX） group （Zn group）. Six rats in each group were randomly chosen at 6, 12 and 24 h after operation to collect blood samples, and then the animals were sacrificed to obtain lung tissues at 24 h after operation. The serum levels of TNF-a, IL-6 and high mobility group box 1 （HMGB1） were determined by ELISA. The expression of HMGB1 mRNA in lung tissues was detected by RT-PCR. Another 40 Wistar rats with the same conditions were grouped according to the method mentioned above and the survival curve was drawn. Re- suits Compared with group C, the serum levels of TNF-a, IL-6 and HMGB1 were significantly increased, the ex- pression of HMGB1 mRNA in lung tissues was up-regulated, and the survival rate was significantly decreased in CLP, Co and Zn groups （P 〈 0.05）. Compared with group CLP, the serum levels of TNF-a, IL-6 and HMGB1 were significantly decreased, the expression of HMGB1 mRNA in lung tissues was down-regulated, and the survival rate was significantly increased in group Co （ P 〈 0.05）, while no significant change was found in the parameters mentioned above in group Zn （ P 〉 0.05）. Conclusion Inducing the expression of HO- 1 is helpful in reducing in- flammatory responses in septic rats.