黄芩汤对溃疡性结肠炎大鼠的保护作用及其影响NF-κB p65蛋白和相关炎症因子表达的机制研究

Protective effect of Huangqin Decoction on UC Rats and mechanism of NF-κB p65 protein and related inflammatory factors

目的:研究黄芩汤对DSS所致溃疡性结肠炎大鼠细胞因子、NF-κBp65蛋白表达的影响,探讨其作用效果及机制。方法:运用右旋葡聚糖硫酸钠(Sodium dextran sulfate,DSS)制备UC大鼠模型,大鼠随机分成正常对照组、模型组、柳氮磺胺吡啶组和黄芩汤高、中、低剂量组。治疗7天后,取结肠组织,评估各组大鼠结肠长度、体重变化及组织损伤程度,采用ELISA法测定结肠组织中肿瘤坏死因子-α(Tumor Necrosis Factor-α,TNF-α)、白介素-6(Interleukin6,IL-6)、白介素-1β(Interleukin1β,IL-1β)含量,运用Western blot法检测NF-κB p65蛋白表达情况。结果:模型组大鼠体重及结肠长度均明显低于正常组大鼠(P<0.01);血清中TNF-α、IL-6、IL-1β水平、结肠组织NF-κB p65蛋白表达量及组织损伤程度显著高于正常组(P<0.01)。与模型组大鼠相比,柳氮磺胺吡啶组大鼠上述指标均减轻,黄芩汤高、中剂量大鼠上述指标较模型组显著改善(P<0.01)。结论:黄芩汤能明显改善模型大鼠精神、体重、肠上皮损伤等,对溃疡性结肠炎的治疗作用可能是通过抑制NF-κB通路活化,进而下调促炎细胞因子TNF-α、IL-6、IL-1β表达实现的。

Objective:To study the effect of Huangqin Decoction on the expression of cytokines,Nuclear factor-kappa b p65(NF-κB p65)in Sodium dextran sulfate(DSS)-induced ulcerative colitis(UC)and its therapeutic effect and mechanism.Method:DSS was used to prepare UC rat models.The rats were randomly divided into normal control group,model group,sulfasalazine group and Huangqin Decoction high,medium and low dose groups.After 7 days of treatment,colon tissue was taken to evaluate the colon length,weight change and tissue damage degree of each group of rats.The tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)and interleukin-1β(IL-1β)content in colon tissue were detected by ELISA method,and the expression of NF-κB p65 protein was detected by Western Blot.Result:The results showed that the weight and the length of the colon in the model group were significantly lower than that in the normal group(P<0.01).Compared with the rats in the model group,serum TNF-α,IL-6,IL-1βlevels,colonic tissue NF-κB p65 protein expression and tissue damage were significantly higher than the normal group(P<0.01).Compared with the model group of rats,the above indicators of the sulfasalazine group were reduced.The above indicators of the rats with high and medium doses of Huangqin Decoction were significantly improved compared with the model group(P<0.01).Conclusion:The effect of Huangqin Decoction can obviously improve the spirit,body weight and intestinal epithelial injury of the model rats.The therapeutic effect on the ulcerative colitis may be realized by inhibiting the activation of the NF-κB pathway,and further down-regulating the expression of the pro-inflammatory cytokines TNF-α,IL-6,IL-1β.