类固醇受体辅活化子-3基因敲除对炎症反应中活化蛋白-1的影响

摘要

目的 观察类固醇受体辅活化子(SRC)-3基因敲除对脂多糖(LPS)诱导的炎症反应中活化蛋白-1(AP-1)表达水平及活性的影响.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20 g,分为SRC-3+/+组和SRC-3-/-组,每组设正常(N)、1 h、4 h、12 h四个时相点,每个时相点各5只小鼠.采用腹腔注射5 mg/kg体质量LPS构建炎症反应动物模型,Western blot测定肝、脾组织c-Jun、c-Fos的蛋白表达.结果 SRC-3+/+组、SRC-3-/-组小鼠肝、脾组织在LPS刺激后c-Jun、c-Fos蛋白表达水平均显著增加,在相应时相点SRC-3-/-组小鼠显著低于SRC-3+/+组.LPS刺激后1、4 h两组小鼠肝组织c-Jun核转位程度显著增加,且SRC-3-/-组仅在1 h显著低于SRC-3+/+组;两组脾组织c-Jun、肝脾组织c-Fos核转位在所有时相点均显著增加,但在相应时相点SRC-3-/-组小鼠均显著低于SRC-3+/+组.结论 LPS刺激后引起AP-1的表达和活性显著增加,SRC-3蛋白缺失可部分抑制AP-1的表达及活性,这可能与致炎细胞因子合成释放减少有关.%Objective To observe the effect of the absence of steroid receptor coactivator (SRC) - 3 on the level of LPS - induced activator protein ( AP) - 1 expression and its activity.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 blot was used to detect the expression of c - Jun and c - Fos in liver and spleen. Results After an intraperitoneal injection of LPS with a dose of 5mg/kg body weight, the level of LPS - induced c - Jun and c - Fos expression in liver and spleen were significantly increased in both SRC - 3+/+ group and SRC -3 -/- group. But at relative time points, it is obviously less in SRC - 3 -/- group than SRC -3 +/+ group. And the nuclear translocation of c - Jun and c - Fos in SRC - 3+/ + mice and SRC -3 -/-group was significantly increased at 1 h and 4 h after LPS stimulation, but the changes in SRC - 3 -/-group were less than those in SRC - 3 +/+ group. Conclusion The expression and activity of AP - 1 are significantly increased after LPS stimulation. The absence of SRC - 3 protein could suppress LPS -induced the expression and activity of AP - 1 owing to relative deficient of the synthesis and release of pro - inflammatory cytokines.