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

摘要

Objective To observe the effect of the absence of steroid receptor coactivator (SRC) - 3 on the expression and aclivily 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 inflammalory response induced by an intraperitoneal injection of LPS (5 mg/kg body weighl) , western blots are used to deled the expression of IkB - α, NF - kB p65/p50 and inlerferon regulatory factor - 1 ( IRF - 1 ) in liver. Results The level of LPS - induced IkB - α expression in liver were significantly downregulaled in both SRC - 3+/+ group and SRC - 3 -/- group. But the downregulalion of IkB - α is more obviously in SRC - 3 +/+ group than SRC - 3 -/- group. After LPS stimulation, the expression and nuclear translocalion of NF - kB p65/p50 in two groups were significantly increased, and the expressions of p65/p50 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 inflammalory response could be regulaled 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 - α degradation and exert suppression on the activity of NF - kB, which may be the mechanisms for it reduce the degree of syslemic inflammatory response.%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-κB(NF-κB)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测定肝组织IκB-α、NF-κB p65/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IκB-α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-κB p65/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-κB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IκB-α降解障碍和NF-κB活性下降所致.