Alpha-黑素细胞刺激素对内毒素血症小鼠肝肺组织表达高迁移率族蛋白1的抑制作用

Inhibitory effect of -melanocyte stimulating hormone on the expression of high mobility group box l in the lungs and livers of mice with endotoxemia

目的研究Alpha-黑素细胞刺激素(α-MSH)对内毒素血症小鼠肝、肺组织中表达高迁移率族蛋白1(HMGB1)的调控作用。方法腹腔内注射(ip)LPS(25g/kg)和D-Gal(100mg/kg)建立内毒素血症小鼠模型,分别在LPS刺激小鼠1、2、3h后腹腔注射α-MSH(2.5mg/kg),24h后处死小鼠,取小鼠肺、脑、脾、肝、肾组织,应用RT-PCR和Westernblot的方法,从基因、蛋白两个水平检测α-MSH对HMGB1表达的调节作用。结果HMGB1mRNA及蛋白在内毒素血症小鼠肺、脑、脾、肝、肾中均有表达,但在肝、肺中的表达量高于其他组织;于LPS刺激小鼠3h之内腹腔注射α-MSH,能显著下调HMGB1mRNA及蛋白的表达,并且1h之内给药效果最理想。结论α-MSH能有效抑制内毒素血症小鼠肝、肺组织中HMGB1的表达。

Objective To evaluate the effect of alpha- melanocyte stimulating hormone（α- MSH ） on the expression of high - mobility group box - 1 （ HMGB1 ） in the lungs and livers of the mice with endotoxemia. Methods Endotoxemia was modeled by endotoxin （ LPS 25 g/kg） and D - Gal （ 100 mg/ kg ） injection intraperitoneally of 6 to 8 - week - old female BALB/c mice. The expression of HMGB1 was tested by RT - PCR and Western blot after treatment with 2.5 mg/kg α- MSH in 1,2,3 h after LPS injection. Result LPS stimulation for 24 h resulted in the high expression of HMGB1 mRNA and protein in the tested organs, including lung, liver, kidney, brain and spleen, from endotoxemia mice, and the expression levels of HMGB1 were higher in the lungs and livers than that in the other organs. HMGB1 expression was markedly reduced in α- MSH ＋ LPS group compared with LPS group, especially the administration of α- MSH in 1 h after LPS injection. Conclusion α- MSH may down - regulate the expression of HMGB1 in the lungs and livers of endotoxemia mice.