类固醇受体辅活化子-3缺失对脂多糖诱导炎症反应的影响  

Effect of the depletion of steroid receptor coactivator - 3 on the inflammatory response induced by LPS

作　　者：李军[1] 粟永萍[1] 王军平[1] 艾国平[1] 刘英海[2] 刘合年[2] 

机构地区：[1]第三军医大学预防医学院复合伤研究所,创伤、烧伤与复合伤国家重点实验室,重庆400038 [2]成都军区总医院麻醉科

出　　处：《中国急救医学》2010年第1期37-39,共3页Chinese Journal of Critical Care Medicine

基　　金：国家重点基础研究发展规划项目（“973”项目）（No.G1999054201）;海外青年学者合作研究基金（No.30328025）;刨伤、烧伤与复合伤国家重点实验室开放基金（No.SKLKF200910）

摘　　要：目的观察类固醇受体辅活化子（SRC）-3蛋白缺失对脂多糖（LPS）诱导炎症反应的影响。方法健康清洁野生型（SRC-3^＋/＋）小鼠、SRC-3基因敲除（SRC-3^-/-）小鼠各20只，雌性，体质量约20g，分为SRC-3^＋/＋组和SRC-3^-/-组，每组设正常（N）、1h、4h、12h四个时相点，每个时相点各5只小鼠。采用腹腔注射5mg／kg体质量LPS构建炎症反应动物模型，观察各时相点重要脏器的病理变化并测定血清TNF-α、IL-1β、IL-6和IL-10浓度。结果LPS腹腔注射后，SRC-3^-/-组小鼠全身情况好于SRC-3^＋/＋组小鼠，但两组的肝、脾、肾、心肌和胸腺病理均未见明显差别。LPS腹腔注射后两组血清TNF—α、IL-1β、IL-6和IL-10的水平均显著升高，但SRC-3^-/-组小鼠血清TNF-α、IL-1β、IL-6水平显著低于SRC-3^＋/＋组小鼠，IL—10水平却显著高于SRC-3^＋/＋组。结论SRC-3蛋白与致炎细胞因子的分泌和释放有关，SRC-3蛋白缺失可减轻炎症反应程度，抑制LPS诱导的TNF-α、IL-1β和IL-6分泌和释放。Objective To observe the effect of the depletion of steroid receptor coactivator （SRC） -3 on the inflammatory response induced by LPS. Methods We use 20 healthy SPF -grade SRC -3 ^＋/＋ mice and SRC - 3^ -/- mice respectively, all of which are female, 20 g and are named SRC -3^＋/＋ group and SRC -3^-/- group. Then we set four phase points： normal, 1 h, 4 h, and 12 h. Each of the phase points has five mice. On the model of inflammatory response induced by an intraperitoneal injection of LPS （5 mg/kg body weight） , the concentration of serum TNF - α, IL - 1β, IL- 6 and IL - 10 were detected and pathological changes of important organ were observed at every phase point. Results After an intraperitoneal injection of LPS with a close of 5mg/kg body weight, general state of health in SRC -3^-/- group was much easier than that of SRC -3^ ＋/＋ group, but no obvious pathological differences were observed in liver, spleen, kidney, cardiac muscle and thymus of the two groups. And after an intraperitoneal injection of LPS, the two groups exhibited a higher expression of serum TNF -α, IL- 1β, IL -6 and IL - 10 than the normal level. But in contrast to the SRC -3 ^＋/＋ group,the serum level of TNF- α,IL- 1β and IL-6 in SRC -3^-/- group was significantly lower than the former group,however,the IL - 10 level significantly higher than that of the former. Conclusion SRC - 3 is related with the synthesis and release of pro - inflammatory cytokines. The depletion of SRC - 3 protein could suppress the release of TNF - α, IL - 1 β IL - 6 of LPS - induced, improve whole body effect during inflammatory reaction.

关 键 词：类固醇受体辅活化子-3 基因敲除 脂多糖 细胞因子 

分 类 号：R322.47[医药卫生—人体解剖和组织胚胎学] R543.2[医药卫生—基础医学]