氯胺酮调节炎症反应中类固醇受体辅活化子的表达

Effect of ketamine on the expression of steroid receptor coactivators in the inflammatory reaction

目的观察脂多糖(LPS)腹腔注射后类固醇受体辅活化子(SRC)家族蛋白表达的早期变化及氯胺酮的影响,探讨氯胺酮调节炎症反应的分子机制。方法将15只健康C57/129雄性小鼠随机分为正常对照组、LPS组、LPS+氯胺酮组,每组5只。LPS 5 mg/kg,腹腔注射；氯胺酮10 mg/kg,肌肉注射,LPS注射后15 min给予。LPS注射后4 h脱臼处死,取肝、脾、肺,采用Western blot测定SRC家族(SRC-1、GRIP-1、NCoA-3)在蛋白水平的变化。结果LPS组与正常对照组相比,肝组织SRC-1蛋向表达水平显著降低,GRIP-1、NCoA-3显著升高；肺组织SRC-1、NCoA -3显著增加,GRIP-1显著降低；脾组织GRIP-1显著降低,NCoA-3显著增加。LPS+氯胺酮组肝组织SRC-1显著高于LPS组,低于正常对照组,肺组织显著低于LPS组,与正常对照组相比明显升高；肝组织GRIP-1显著低于LPS组,高于正常对照组,而脾、肺组织显著增加,与正常对照组相比无显著差别；NCoA-3蛋白表达水平显著低于LPS组,脾、肺组织明显高于正常对照组,而肝组织相差不显著。结论LPS刺激下肝、脾、肺组织SRC家族成员的变化不同,氯胺酮可抑制LPS诱导的SRC表达变化,其对炎症反应的抑制可能是一种间接作用。

Objective To evaluate the effect of ketamine on the expression of steroid receptor coactivators during the early stage in rats with LPS injection. Methods 15 C57/129 male mice were divided randomly into three groups： normal control; LPS, receiving an intraperitonea/ injection of 5 mg/kg LPS; and LPS ＋ ketamine, receiving an intramuscular injection of 10 mg/kg ketamine initiated 15 min after LPS injection. All the rats were killed after 4 h LPS injection, the levels of hepatic, splenic and pul- monary SRC - 1, GRIP - 1, NCoA -3 were detected by Western blot. Results After LPS injection, the level of hepatic SRC - 1, splenic and pulmonary GRIP - 1 were obviously increased compared with normal control group. In LPS ＋ ketamine group, hepatic SRC - 1, splenic and pulmonary GRIP - 1 were obviously higher and hepatic GRIP - 1 and NCoA - 3, pulmonary SRC - 1, NCoA - 3 and splenic NCoA - 3 were markedly lower than LPS group, but hepatic SRC - 1 was markedly decreased, pulmonary SRC - 1, hepatic GRIP - 1, pulmonary and splenic NCoA -3 were significantly elevated compared with normal control group. The hepatic NCoA - 3, pulmonary and splenic GRIP - 1 in LPS ＋ ketamine group were no signifi- cant difference with normal control group. Conclusion These results indicate that the expression of is different during the early stage in the hepatic, splenic and pulmonary tissue in LPS induced mice. Ketamine could not directly effect on inflammatory reaction, could suppress these changes of steroid receptor coactivators of LPS induced.