机构地区:[1]解放军第三O四医院创伤外科中心免疫研究室,北京100037
出 处:《中华创伤杂志》2002年第9期540-543,共4页Chinese Journal of Trauma
基 金:国家重点基础研究发展规划资助项目 (G19990 5 42 0 3 );国家杰出青年科学基金资助项目(3 0 12 5 0 2 0 );军队杰出中青年人才专项基金资助项目 (98J0 13 );军队"十五"医药卫生科研基金资助项目(0 1MA2 0 7)
摘 要:目的 探讨脓毒症时组织脂多糖结合蛋白 (LBP)和脂多糖受体CD14的改变及其与高迁移率族蛋白 - 1(HMG - 1)诱生的关系。 方法 采用大鼠盲肠结扎穿孔 (CLP)致脓毒症模型 ,大鼠随机分成正常对照组、假手术组、CLP组及杀菌 通透性增加蛋白治疗组 (rBPI2 1治疗组 )。检测肝、肺、肾和小肠组织LBP、CD14及HMG - 1基因表达的变化。 结果 CLP组术后 2h ,肝、肺、肾和小肠组织LBP CD14mRNA表达均有不同程度增高 (P <0 .0 5~ 0 .0 1)。与CLP组比较 ,rB PI2 1治疗组CLP后 12h和 2 4h肝、肺组织LBPmRNA表达明显受抑制 (P <0 .0 1) ,12h各组织及2 4h小肠CD14mRNA表达亦明显降低 (P <0 .0 5 )。同时 ,CLP组术后 6h肝、肺、小肠HMG - 1mR NA表达显著增高 (P <0 .0 5 ) ,2 4h达峰值 (P <0 .0 1) ,并持续至 72h。rBPI2 1早期治疗可显著降低12h各组织和 2 4h肝、小肠HMG - 1mRNA的表达。相关分析表明 ,CLP后肝、肺、肾及小肠组织LBP CD14mRNA表达与相应组织的HMG - 1mRNA表达均呈显著正相关。 结论 脓毒症时LBP CD14增敏系统可能参与了晚期炎症介质HMG - 1的诱生过程。Objective To investigate expression changes of tissue lipopolysaccharide binding protein/CD14 (LBP/CD14) mRNA and its relation with high mobility group 1 (HMG 1) formation in septic rats. Methods Using a sepsis model by cecal ligation puncture (CLP), 100 male Wistar rats were randomly divided into four groups: normal control group (n=10), sham operation group (n=10), CLP group (divided into 2, 6, 12, 24, 48 and 72 hours post CLP subgroups, n=60), and bactericidal/permeability increasing protein (rBPI21) treatment group (divided into 12 and 24 hours post CLP subgroups, n=20). At serial time points in each group, animals were sacrificed, and tissue samples from the liver, the lungs, the kidneys and the intestine were harvested to determine LBP/CD14 and HMG 1 mRNA expressions by reverse transcription polymerase chain reaction (RT PCR). Results LBP/CD14 mRNA levels markedly increased in various tissues at the 2 hour after CLP ( P <0.05 0.01). LBP mRNA expression was significantly inhibited by rBPI21 at 12 hours and 24 hours in the liver and the lungs ( P <0.05), CD14 mRNA expression was also decreased at 12 hours in various tissues and at 24 hours in intestine. Meanwhile, HMG 1 mRNA expression was significantly enhanced in the liver, the lungs and the intestine at 6 hours after CLP ( P <0.05 0.01), peaked at 24 hours and kept relative high values up to 72 hours compared with normal controls. Early treatment with rBPI21 could significantly reduce HMG 1mRNA levels at 12 hours in various tissues and at 24 hours in the liver and the intestine. Furthermore, LBP/CD14 mRNA expressions in the liver, the lungs, the kidneys and the intestine were positively correlated with HMG 1 in corresponding tissues ( P <0.01). Conclusions These data suggest that excessive LBP/CD14 expression in vital organs may be involved in an up regulation of HMG 1 gene expression in CLP induced sepsis.
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