Zhang Li-tian, Yao Yong-ming, Lu Jia-qi, Dong Ning, Yu Yan, Yan Xiao-jian, Fang Wen-hui, Sheng Zhi-yong
Trauma Research Center, 304th Hospital of People's Liberation Army, Beijing 100037, China.
Zhonghua Wai Ke Za Zhi. 2003 Apr;41(4):303-6.
To investigate the potential role of high mobility group-1 protein (HMG-1) in the pathogenesis of sepsis-induced multiple organ dysfunction syndrome in rats.
Using a sepsis model by cecal ligation and puncture (CLP), 80 male Wistar rats were randomly divided into four groups: normal control (n = 10), sham operation (n = 10), CLP (subdivided into 2, 6, 12, 24, 48, 72 h post-CLP, n = 60), and sodium butyrate treatment (subdivided into 12, 24 h post-CLP, n = 20). At serial time points in each group, animals were sacrificed, and blood as well as tissue samples from the liver, lung, kidney and small intestine were harvested to measure organ function parameters and HMG-1 mRNA expression by the reverse transcription polymerase chain reaction (RT-PCR) taking GAPDH as an internal standard. Also, additional experiments were performed to observe the effect of treatment with sodium butyrate on survival rate in septic rats (n = 57).
HMG-1 mRNA levels significantly increased in various tissues during 6 - 72 h after CLP (P < 0.05 or 0.01), and were markedly inhibited by sodium butyrate at 12 h and 24 h (P < 0.05 or 0.01). Early treatment with sodium butyrate also could markedly reduce serum alanine aminotransferase, creatinine levels at 12 h post-CLP and pulmonary myeloperoxidase activities at 24 h. Furthermore, treatment with sodium butyrate could significantly improve the 1- to 6-day survival rates in animals subjected to CLP (P < 0.05 or 0.01).
HMG-1 might play an important role in the development of excessive inflammatory response and subsequent multiple organ dysfunction syndrome.
探讨高迁移率族蛋白1(HMG-1)在大鼠脓毒症诱导的多器官功能障碍综合征发病机制中的潜在作用。
采用盲肠结扎穿孔(CLP)制备脓毒症模型,80只雄性Wistar大鼠随机分为四组:正常对照组(n = 10)、假手术组(n = 10)、CLP组(再分为CLP术后2、6、12、24、48、72小时组,n = 60)和丁酸钠治疗组(再分为CLP术后12、24小时组,n = 20)。在每组的连续时间点处死动物,采集血液以及肝脏、肺、肾和小肠的组织样本,以甘油醛-3-磷酸脱氢酶(GAPDH)为内参,通过逆转录聚合酶链反应(RT-PCR)检测器官功能参数和HMG-1 mRNA表达。此外,进行额外实验观察丁酸钠治疗对脓毒症大鼠存活率的影响(n = 57)。
CLP术后6 - 72小时,各组织中HMG-1 mRNA水平显著升高(P < 0.05或0.01),丁酸钠在12小时和24小时显著抑制其表达(P < 0.05或0.01)。丁酸钠早期治疗还可显著降低CLP术后12小时的血清丙氨酸氨基转移酶、肌酐水平以及24小时的肺髓过氧化物酶活性。此外,丁酸钠治疗可显著提高CLP动物1至6天的存活率(P < 0.05或0.01)。
HMG-1可能在过度炎症反应及随后的多器官功能障碍综合征的发生发展中起重要作用。