类固醇受体辅活化子-3缺失对核因子-κB表达及活性的影响  

Effect of absence of steroid receptor coactivator - 3 on the expression and activity of NF - KB

作　　者：李军[1] 牛洁[1] 刘英海[1] 汪海洋[1] 粟永萍[2] 王军平[2] 

机构地区：[1]成都军区总医院麻醉科,成都610083 [2]第三军医大学中国人民解放军复合伤研究所,创伤、烧伤与复合伤国家重点实验室,重庆400038

出　　处：《中国急救医学》2011年第10期897-900,共4页Chinese Journal of Critical Care Medicine

基　　金：创伤、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）诱导的炎症反应中核因子-KB（NF—KB）表达及活性的影响。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，Westernblot测定肝组织IKB-α、NF—KBp65／p50和干扰素调控因子-1（IRF-1）的蛋白表达。结果LPS刺激后早期两组小鼠肝组织IKB—d蛋白水平显著降低，其中SRC-3＊/＊组小鼠下降更明显；两组小鼠肝组织NF—KBp65／p50蛋白表达和核转位程度均显著增加，其蛋白表达水平SRC-3。组小鼠高于SRC-3＋/＋组，而核转位程度却显著低于SRC-3＊/＊组；无论是SRC-3＋/＋组还是SRC-3。-组小鼠，LPS刺激引起IRF-1蛋白表达水平显著增加，在相应时相点SRC-3。-组小鼠均显著低于SRC-3＋/＋组。结论SRC-3可通过干预NF—KB的活性来调控炎症反应，其蛋白缺失减轻炎症反应程度可能是其导致IKB—α降解障碍和NF—KB活性下降所致。Objective To observe the effect of the absence of steroid receptor coactivator （SRC） - 3 on the expression and activity of nuclear factor - kappa B （ NF - KB ） during LPS - induced inflammatory response. 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 ）, western blots are used to detect the expression of IKB - a, NF - KB p65/pSO and interferon regulatory factor - 1 （ IRF - 1 ） in liver. Results The level of LPS - induced IKB - a expression in liver were significantly downregulated in both SRC- 3 ＋/＋ group and SRC- 3-/- group. But the downregulation of IKB - a is more obviously in SRC - 3 ＋/- group than SRC - 3 -/ group. After LPS stimulation, the expression and nuclear translocation of NF - KB p65/pSO in two groups were significantly increased, and the expressions of p65/pSO in SRC -3 -/- group were significant higher than those in SRC -3 ＋/- group but the nuclear translocation of them in SRC -3 -/- group were markedly less than those in SRC - 3＋/＋ group. In two groups, the LPS - induced IRF - 1 expressions were significantly markedly elevated compare with normal control. But at relative time points, it is obviously less in SRC - 3 -/- group than SRC - 3 ＋ / ＋ group. Conclusion The inflammatory response could be regulated by SRC - 3 protein which can affect the activity of NF - KB. The absence of SRC - 3 protein can result in relative deficient of IKB - a degradation and exert suppression on the activity of NF - kB, which may be the mechanisms for it reduce the degree of systemic inflammatory response.

关 键 词：类固醇受体辅活化子-3 基因敲除 脂多糖 炎症反应 核因子-KB 

分 类 号：R363.2[医药卫生—病理学]