Pim-1抑制剂对小鼠溃疡性结肠炎的治疗作用及机制研究

Mechanism of Pim-1kinase inhibitor therapeutic potentials in acute ulcerative colitis

目的探讨Pim-1抑制剂(PIM-Inh)对小鼠溃疡性结肠炎的治疗作用及机制研究。方法 BALB/C小鼠40只随机分组,分别为正常对照组、模型组、低PIM-Inh治疗组、高PIM-Inh治疗组,第8日处死小鼠,进行疾病活动指数(DAI)评分及病理组织学评分,并采用酶联免疫吸附法(ELISA)测定各组肠组织中IFN-γ、IL-4、TGF-β、IL-17的表达。结果 PIM-Inh治疗组DAI评分及组织学评分均较模型组有明显下降。PIM-Inh可以显著降低肠组织中IFN-γ、IL-17的表达,且呈剂量依赖性。结论 PIM-Inh对实验性小鼠溃疡性结肠炎具有治疗作用,可能与抑制IFN-γ、IL-17的表达有关。

Objective To assess whether blocking Pim-1 kinase may be of therapeutic benefit as a treatment regimen for ulcerative colitis. Methods Mice with acute colitis induced by 5% DSS were treated with or without PIM-Inh, DAI and colon inflammation were evaluated, and production of lymphocytes cytokines（IFN-γ, IL-4, TGF-β, IL-17） in colon tissues was determined by ELSIA. Results the PIM-Inh had protective and therapeutic potentials in acute DSS colitis in vivo, treatment with PIM-Inh inhibited the production of IFN-γ and IL-17 in a dose-dependent manner. Conclusion We found that PIM-Inh reduced the proinflammatory immune response through down-regulation of excessive IFN-γ and IL-17.