【作者】 刘朝霞；

【导师】 谢晶日；

【作者基本信息】 黑龙江中医药大学 ， 中医内科学， 2009， 博士

【摘要】 目的探讨溃疡性结肠炎(UC)的基本病机，研究以清热解毒、健脾燥湿为立法原则所创立的经验方剂肠愈宁对活动期UC细胞网络因子TLR4，NF-κB，TNF-α的调控作用，阐明肠愈宁治疗活动期溃疡性结肠的作用机制。方法采用改良复合法(2，4二硝基氯苯(DNCB)、乙酸+高脂饮食)造模方法制作符合湿热蕴结型的UC大鼠模型，并采用具有清热解毒、健脾燥湿功效的中药肠愈宁颗粒进行治疗。治疗时，分别给予低剂量(1 0g／kg·d)和高剂量(20g／kg·d)的肠愈宁颗粒灌胃，并以西药SAS P(0．5g／k g·d)作为阳性对照药，同时设模型组和空白组进行对照。造模时间为1 6天，造模成功后给予治疗4周。造模期间及治疗结束后分别观察炎症活动指数(DAI)。并于治疗结束后处死大鼠，进行炎症大体形态损伤评分，组织学损伤评分，观察肠黏膜病理变化情况，以及对组织TNF-α、TLR 4，NF-κB的影响。结果统计学分析认为西药组、中药低剂量组、中药高剂量组与模型对照组比较有显著性差异(P＜0．01)，而西药组、中药低剂量组、中药高剂量组三组无明显差异，说明肠愈宁颗粒与柳氮磺胺吡啶对UC大鼠均具有治疗作用；西药组、中药低剂量组、中药高剂量组与模型对照组比较有显著性差异(P＜0．01)，说明肠愈宁对UC细胞网络因子TLR 4，NF-κB，TNF-α有调节作用。结论1．活动期UC的中医病机主要为湿热蕴结兼有脾虚，湿热蕴结是UC活动期的病理特点，脾虚是UC的发病基础和必然转归。2．大鼠结肠黏膜的细胞网络因子TLR 4、NF-κB、TN F-α在UC活动期处于高表达，可能是UC发病的重要机制。3．肠愈宁对活动期UC大鼠模型有治疗作用，对于DAI评分、大体评分及炎症评分都有显著的降低作用。4．肠愈宁对活动期溃疡性结肠炎大鼠黏膜中的TNF-α的表达有抑制作用。5．肠愈宁对活动期溃疡性结肠炎大鼠黏膜中的TLR 4的表达有抑制作用。6．肠愈宁对活动期溃疡性结肠炎大鼠黏膜中的NF-κB的表达有抑制作用。7．肠愈宁对活动期UC大鼠结肠黏膜的细胞网络因子有调控作用，该作用可能是肠愈宁颗粒治疗UC的主要机制之一。更多还原

【Abstract】 Objective:Discussing the basic pathogenesis of ulcerative colitis andinvestigate the regulating effects on cytokine network factorsTLR4,NF-kB,TNF-a of active ulcerative colitis in rats,with Chang Yu NingGranula,a experiential decoction which was formed basing on rule ofclearing away heat to detoxify and strengthening spleen to removedampness,in order to clarify the functional mechanism of Chang Yu NingGranula on treating active ulcerative colitis.Methods:Making rats models which according to the syndrome ofaccumulation of dame-heat by using composite methods and then treatingthem with Chang Yu Ning Granula.Both of the two Chinese medicinetreating groups were given high dose and low dose of Chang Yu NingGranula separately.The control group was treated with SASP,meanwhile,there are also model group and blank group for comparison.The treatinggroup was administrated for 4 weeks after successfully making rats modelsfor 16 days.Inflammatory activity index(DAI)was assessed during modelsmaking period and after treatment.The tissues from rats models wereobserved under optical microscope,in order to know the change or gastricmucosa and the pathological and histological injury,then the expression ofTLR4,NF-kB and TNF-a were detected in tissues with Elisa methods andRT-PCR respectively.Result:Results:It is indicated by statistical analysis that the scores ofDAI,histological injury,and general morphological damage weresignificantly different in blank control group,control group,westernmedicine group,low dose of Chinese medicine group and high dose ofChinese medicine group.(p＜0.01),There weren’t obvious difference amongwestern medicine group,low dose group of Chinese medicine and high dosegroup of Chinese medicine.It shows that both of Chang Yu Ning Granulaand SASP have therapeutic effect with UC.and Chang Yu Ning Granula has regulating function on cytokine network factors TLR4,NF-kB and TNF-a.Conclusion:1.The basic pathogenesis of active UC is mainlyaccumulation of damp-heat accompany with deficiency of spleen.Accumulation of damp-heat is the pathological characteristic of active UCand deficiency of spleen is basic pathogenesis and inevitable outcome.2.Cytokine network factors TLR4,NF-kB and TNF-a in rats colonic mucosahave high expression in active UC,which may be important mechanism ofincidence of UC.3.Chang Yu Ning Granula has therapeutic effects on activeUC,and can also low down the score of DAI,general morphology andinflammation.4.Chang Yu Ning Granula has inhibition function on theexpression of TLR4 in rats colonic mucosa of active UC.5.Chang Yu NingGranula has inhibition function on the expression of TNF-a in rats colonicmucosa of active UC.6.Chang Yu Ning Granula has inhibition function onthe expression of NF-kB in rats colonic mucosa of active UC.7.Chang YuNing Granula has regulating function on expression of cytokine networkfactors in rats colonic mucosa of active UC,which is the main mechanismof Chang Yu Ning Granula on treating UC.更多还原