雷公藤多苷对溃疡性结肠炎小鼠结肠组织MIF及TLR 4的影响

Effects of Tripterygium glycosides on MIF and TLR4 in colonic tissue of mice with ulcerative colitis

目的观察雷公藤多苷对溃疡性结肠炎(ulcerative colitis,UC)小鼠结肠组织巨噬细胞游走抑制因子(MIF)和Toll样受体4(Toll-like receptor,TLR4)的影响。方法按照随机原则将BALB/c小鼠分为正常对照组、模型对照组和雷公藤多苷低、中、高剂量组。采用右旋葡聚糖硫酸钠法(DSS)复制BALB/c小鼠溃疡性结肠炎模型。正常对照组小鼠自由饮水,其余各组小鼠每日灌胃给药1次,连续7 d。模型对照组予生理盐水0.4 m L灌胃,不同剂量雷公藤多苷组分别以9.00、27.03和81.09 mg/kg浓度的雷公藤多苷混悬液0.40 m L灌胃,实验期间每天观察小鼠一般情况,末次给药后解剖观察,组织切片染色,光镜下观察结肠组织的病理学变化,采用ELISA酶联法检测结肠组织匀浆蛋白MIF的含量,以荧光定量PCR检测结肠黏膜TLR4 m RNA表达。结果模型对照组小鼠结肠组织中MIF含量和TLR4 m RNA水平较正常对照组明显上升,而不同剂量雷公藤多苷组小鼠结肠组织中MIF含量较模型对照组明显下降(P<0.01),TLR4 m RNA表达显著降低(P<0.01)。结论雷公藤多苷通过降低MIF含量,进而降低TLR4 m RNA表达,影响TLR4信号通路,从而达到抗溃疡性结肠炎的作用。

Objective To observe the effects of Tripterygium glycosides on the migration of macrophage migration inhibitory factor（MIF） and toll-like receptor 4（TLR4） in colonic tissue of mice with ulcerative colitis.Methods BALB/c mice were randomly divided into normal control group,model control group and low,medium and high doses of Tripterygium glycosides groups.Ulcerative colitis model of BALB/c mice was replicated by dextran sodium sulfate method（DSS）.The normal control group had free access to water,the remaining groups were administered intragastrically once a day for 7 days.The model control group was given normal saline 0.40 m L through intragastric administration.Different dose groups were given 0.4 m L of 9.00,27.03 and 81.09 mg/kg tripterygium glycosides suspension through intragastric administration.General status of mice were observed daily during the experiment.After the last administration,we conducted anatomical observation and histological section staining to colonic tissue,and pathological changes of colonic tissue were observed under light microscope.The contents of MIF in colonic tissue were detected by enzyme-linked immunosorbent assay（ELISA）,and the expression of TLR4 m RNA in colonic mucosa was detected by fluorogenic quantitative PCR.Results MIF and TLR4 m RNA level in colonic tissues of model control group were significantly increased compared with those of normal control group.MIF levels in colonic tissues of different doses of tripterygium glycosides group were significantly lower than those of model control group（P〈0.01）,and TLR4 m RNA expression was significantly reduced（P〈0.01）.Conclusion Tripterygium glycosides can reduce MIF level,and then inhibit the expression of TLR4 m RNA and TLR4 signaling pathway,thereby achieving the effect of anti-ulcerative colitis.