摘要
目的观察正丁酸钠对严重脓毒症时多器官高迁移率族蛋白B1(HMGB1)基因表达的影响及意义.方法采用大鼠盲肠结扎穿孔(CLP)造成脓毒症模型.动物分为正常对照组(n=10)、假手术组(n=10)、盲肠结扎穿孔组(n=20)及正丁酸钠治疗组(n=20).留取肝、肺、肾及小肠组织和血标本,分别检测HMGB1 mRNA表达及各器官功能指标;同时观察正丁酸钠对脓毒症大鼠的治疗效果(n=57).结果正丁酸钠处理可显著降低腹腔感染后12及24h大鼠肝、肺、肾及小肠等组织HMGB1 mRNA表达,感染后12h血清丙氨酸转氨酶、肌酐水平比未治疗组显著降低(P<0.01),24h肺组织髓过氧化物酶活性亦明显下降(P<0.01).早期给予正丁酸钠治疗,大鼠1～6天存活率显著高于未治疗组(P<0.05或0.01). 结论正丁酸钠对晚期致炎因子HMGB1介导的炎症反应具有潜在的治疗作用.
Objective To investigate the effects and significance of administration of sodium butyrate, a short chain fatty acid, on inhibiting the expression of high mobility group box 1 protein （HMGB1） in rats with impending sepsis. Methods Sepsis rat model was reproduced by cecal ligation puncture （CLP）. 60 male Wistar rats were randomly divided into four groups as follows： normal control group （n= 10）, sham operation group （n= 10）, CLP group （n=20, further divided into 12h and 24h post-CLP subgroups, 10 rats for each subgroup）, and sodium butyrate treatment group （n=20, further divided into 12h and 24h post-CLP subgroups, 10 rats for each subgroup）. At the two time points animals in all groups were sacrificed, and meanwhile, blood and tissue samples from liver, lungs, kidneys and small intestine were harvested to determine parameters of the organ functions, and RT-PCR taking GAPDH as the internal standard was used to detect the expression of HMGB1 mRNA. Additional experiment was performed to observe the treatment effects of sodium butyrate on septic rats （n=57）. Results After the cecal ligation puncture, HMGB1 mRNA levels significantly increased in the liver, lungs, kidneys and intestine, while the increases were effectively suppressed by the use of sodium butyrate （P〈0.05-0.01）. Earlier treatment using sodium butyrate may markedly reduce both the serum alanine transaminase （ALT） and creatinine （Cr） levels at 12h, and the activity of pulmonary myeloperoxidase （MPO） was also suppressed at 24h post-CLP. Furthermore, treatment with sodium butyrate could significantly improve the 1～6 days＇ survival in animals subjected to CLP （P〈0.05-0.01）. Conclusions Sodium butyrate might have therapeutic potential for systemic inflammation mediated by HMGB1.
出处
《解放军医学杂志》
CAS
CSCD
北大核心
2005年第10期867-869,共3页
Medical Journal of Chinese People's Liberation Army
基金
国家重点基础研究发展规划项目(编号G1999054203
2005CB522602)
国家杰出青年基金课题(编号30125020)
军队十五医药卫生科研课题(编号01MA207)
