摘要
目的:观察芍黄安肠汤(SAD)对UC大鼠模型Toll样受体4(TLR4)/髓样分化因子88(MyD88)/核因子-κB(NF-κB)信号通路的干预作用,对其治疗UC的作用机制进行探讨。方法:采用三硝基苯磺酸/无水乙醇灌肠法诱导UC大鼠模型。将60只SD大鼠随机分为正常组、模型组、SAD低、中、高剂量组(4.5,9,18 g·kg-1)、美沙拉嗪组(0.5 g·kg-1),每组各10只。造模后第2天,用药组分别给予相应药物连续灌胃10 d。观察UC大鼠疾病活动指数(DAI)、结肠大体形态损伤以及组织学评分,采用免疫组化的方法观察UC大鼠肠道组织核因子-κB(NF-κB)表达,RT-PCR法检测Toll样受体4(TLR4)和髓样分化因子88(MyD88)mRNA的表达。结果:模型组大鼠的DAI、结肠大体形态损伤及组织学评分均显著高于正常对照组(P<0.05)。芍黄安肠汤各剂量组的DAI评分、结肠大体形态损伤评分低于模型组(P<0.05);与正常组相比,其余各组大鼠NF-κB,TLR4mRNA,MyD88 mRNA表达明显增强(P<0.05);芍黄安肠汤各剂量组和美沙拉嗪组较模型组大鼠上述指标明显降低(P<0.05)。结论:芍黄安肠汤对UC有较好的疗效,其作用机制可能是抑制TLR4的表达,影响MyD88引发信号通路下游的基因表达,从而抑制NF-κB的活化,最终减轻机体炎症反应。
Objective： To observe the effect of Shaohuang Anchang decoction （SAD） on Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-κB（NF-κB） in colonic mucosa of rats with ulcerative colitis（UC）, and to explore its possible mechanism. Method： The rat UC model was induced by trinitro-benzene-sulfonic acid （TNBS）/anhydrous alcohol.The SD rats were randomized into the normal group, model group, SAD low-dose group, SAD middle-dose group, SAD high-dose group （4.5,9,18 g·kg^-1）and the Mesalazine group（5 g·kg^-1）, with 10 in each. Since the 2nd day of modeling,corresponding medications were respectively administered to each treatment group by gastrogavage for 10 successive days.Disease activity index （DAI）, colon macroscopic damage score （CMDS） were calculated, The expression of NF-κB in the colonic mucosa was detected by immunohistochemistry.The expressions of TLR4 mRNA and MyD88 mRNA were detected with reverse transcription-polymerase chain reaction. Result： Compared with the normal group, the model group showed significantly increased DAI, CMDS, but the SAD groups showed more lower than the model group. Compared with the normal group, the expressions of NF-κB, TLR4 mRNA, MyD88 mRNA were significantly increased in other groups. Comparing with the control group, the expressions of NF-κB, TLR4 mRNA, MyD88 mRNA were significantly decreased in the SAD low-dose, middle-dose, high-dose groups and the Mesalazine group, especially in the SAD high-dose group. Conclusion： Treatment with DG could reduce inflammatory injury in rats with ulcerative colitis. Its possible mechanism may be through inhibiting the expression of TLR4 and then inhibiting the activation of MyD88 and NF-κB, and finally reducing inflammatory reaction.
出处
《中国实验方剂学杂志》
CAS
北大核心
2014年第7期151-155,共5页
Chinese Journal of Experimental Traditional Medical Formulae
基金
高等学校博士学科点专项科研基金(20093237110005)
