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

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20 g,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5 mg/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.

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

Objective To observe the effect of the depletion of steroid receptor coactivator (SRC) -3 on the inflammatory response induced by LPS.Methods We use 20healthy 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, 1h, 4h, and 12h.Each of the phase pointshas 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 dose of 5mg/kg body weight, general state ofhealth 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 ahigher 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 I L-6 in SRC -3~(-/-) group was significantly lower than the former group,however,the IL -10 level significantlyhigher 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-1β, IL-6 of LPS -induced, improve whole body effect during inflammatory reaction.