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左金丸阻断溃疡性结肠炎小鼠NF-κB激活MIF、TNF-α及IL-1β、IL-6表达
Studies of Zuojinwan blocking NF-κB activation on the expressions of MIF,TNF-α,IL-1β and IL-6 in the ulcerative colitis mice
【摘要】 目的:研究左金丸阻断溃疡性结肠炎(UC)模型小鼠核因子-κB(NF-κB)激活巨噬细胞移动抑制因子(MIF)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)表达的影响。方法:2.4.6-三硝基苯磺酸复制UC模型,用左金丸水煎液(3.0和6.0g/kg)和柳氮磺吡啶肠溶片(0.1g/kg)灌胃给药,每天1次,连续3周,观察实验小鼠一般状况。3周后检测,眼球取血,进行血液中TNF-α、IL-1β和IL-6含量分析;取结肠组织进行组织形态学分析;实时定量PCR检测结肠组织中MIF及对应的受体CD74基因表达,Western blot检测结肠组织中NF-κBp65蛋白表达。结果:左金丸(3.0和6.0g/kg)和柳氮磺吡啶肠溶片(0.1g/kg)可显著改善UC模型小鼠的一般状况,降低血液中促炎因子TNF-α、IL-1β和IL-6含量及结肠组织中MIF、CD74和NF-κBp65的基因和蛋白表达,减轻促炎因子对结肠造成的损伤,其中以左金丸6.0g/kg剂量组作用效果更为显著。结论:左金丸对UC结肠中各细胞因子的表达具有重要的抑制效应,阻断NF-κB信号通路可能对于UC具有潜在治疗价值。
【Abstract】 Objective:To investigate Zuojinwan blocking nuclear factor-κB(NF-κB) activation on the expressions of macrophage migration inhibitory factor(MIF),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6) in the ulcerative colitis mice.Methods:The ulcerative colitis(UC) model was established through colon administration of 2,4,6-three trinitrobenzene sulfonic acid.Therapeutic groups were given water decoction from Zuojinwan(3.0 and 6.0g/kg) and and Sulfasalazine enteric-coated tablet(0.1g/kg),once a day,for three weeks,the general condition of mice was observed.After oral administration of Zuojinwan for three weeks,the serum levels of TNF-α,IL-1β,and IL-6 were measured;Colonic tissue morphology were analyzed by HE staining;Real-time PCR was applied to detect the mRNA expressions of MIF and corresponding receptor CD74,protein expression of NF-κBp65 in colonic tissue were detected by western blotting.Results:Zuojinwan(3.0 and 6.0g/kg) and Sulfasalazine enteric-coated tablet(0.1g/kg) might significantly improve the general condition of the ulcerative colitis mice,decrease the contents of serum TNF-α,IL-1β,IL-6,the mRNA and protein expressions of MIF,CD74 and NF-κBp65 in colnoic tissue(P < 0.05,P < 0.01,respectively),alleviate the proinflammatory cytokine on colonic injury,especially Zuojinwan 6.0g/kg/day group.Conclusion:Zuojinwan has an important inhibitory effect on the expression of each cytokine in UC,blocking NF-κB signaling pathway for UC may have potential therapeutic value.
【Key words】 Zuojinwan(左金丸); ulcerative colitis; nuclear factor-κB; macrophage migration inhibitory factor; proinflammatory cytokine;
- 【文献出处】 中药药理与临床 ,Pharmacology and Clinics of Chinese Materia Medica , 编辑部邮箱 ,2014年06期
- 【分类号】R285
- 【被引频次】19
- 【下载频次】591