乌梅丸及其拆方对溃疡性结肠炎大鼠细胞因子、炎性介质及TLR4/NF-κB信号通路影响的实验研究
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摘要
目的：观察乌梅丸及其拆方对溃疡性结肠炎大鼠细胞因子、炎性介质、TLR4/NF-KB信号通路以及胃肠功能的影响和对乙酸诱导小鼠腹痛的影响,分析乌梅丸及不同药物配伍治疗溃疡性结肠炎的作用靶点和作用机制,探讨该方寒热配伍在治疗溃疡性结肠炎中的作用,揭示寒热不同属性药物组之间的协同或制约作用。
方法：①雄性SD大鼠,采用大承气汤合TNBS/乙醇复制寒热错杂型溃疡性结肠炎动物模型,8h后给予乌梅丸拆方灌胃,12d后处死大鼠,检测胃肠功能、血常规,光镜观察结肠组织病理学变化,EL1SA法检测结肠组织TNF-α、PGE2、IL-1、IL-10、MPO、PAF含量；RT-PCR检测结肠组织TLR4、MYD88、NF-KBmRNA的表达,黄嘌呤氧化酶法测定结肠组织和血清SOD活性。②雌雄各半昆明小鼠,各组给予乌梅丸拆方灌胃给药,30min后,腹腔均注射0.6%乙酸溶液0.2ml/只,记录注射后30min内出现的扭体反应次数,最早扭体出现时间,计算平均扭体次数、镇痛率,连续观察5d。
结果：①一般行为表现：全方组、寒热并用组的精神状态、饮食、皮毛色泽、体重等情况较模型组明显改善,且全方组、寒热并用组优于其余各组。②病理形态学观察：模型组大鼠结肠粘膜表面起伏不平,可见大量炎性细胞浸润,腺体萎缩,排列紊乱,杯状细胞形态改变,有隐窝脓肿形成,可见溃疡面或粘膜大面积缺损,严重的甚至损害粘膜下层,表现为粘膜下层大量炎性细胞浸润。给药治疗后,全方组及寒热并用组上述病理改变明显减轻,其余各组仍可见炎性细胞浸润等炎症表现。③血清白细胞计数,结肠组织IL-1、TNF-α、MPO含量：与空白组比较,血清白细胞计数,结肠组织IL-1、TNF-a、MPO含量显著升高,全方组、寒热并用组、温热组、寒凉组和补益组明显降低(P<0.01)；与全方组比较,寒热并用组、寒凉组、温热组和补益组有显著性差异(P<0.01)。④血清SOD和结肠组织PGE、IL-10含量、SOD活性：与空白组比较,模型组大鼠结肠组织PGE2含量升高,IL-10含量和SOD活性降低,全方组、寒热并用组、温热组和补益组大鼠结肠组织PGE2显著降低,IL-10含量和SOD活性显著升高(P<0.01),寒凉组、收敛组无差异(P>0.05)。⑤结肠组织PAF含量：与空白组比较,模型组大鼠结肠组织PAF含量显著升高,全方组、寒热并用组、温热组显著降低(P<0.01),寒凉组降低(P<0.05)；与全方组比较,寒凉组有显著性差异(P<0.01)。⑥大鼠结肠组织TLR4、MYD88、NF-κBmRNA表达：与空白组比较,模型组大鼠结肠组织TLR4、MYD88、NF-κBmRNA表达显著增强(P<0.01)。全方组和寒热并用组表达明显降低(P<0.01),温热组和寒凉组表达降低(P<0.05)；与全方组比较,寒热并用组无差异(P>0.05)。⑦大鼠胃残留率和小肠推进率：与空白组比较,模型组大鼠胃残留率明显升高,小肠推进率降低(P<0.01)。全方组、寒热并用组、温热组胃残留率降低,小肠推进率升高,有显著性差异(P<0.01),收敛组胃残留率升高,小肠推进率降低(P<0.01)；与全方组比较,寒热并用组和温热组无差异(P>0.05)。⑧最早扭体时间,平均扭体次数：与模型组比较,全方组、寒热并用组和温热组最早扭体时间延长,平均扭体次数降低(P<0.01),收敛组和补益组平均扭体次数降低(P<0.01)；寒凉组无差异(P>0.05)；与全方组比较,寒热并用组和温热组无差异(P>0.05)。
结论：①乌梅丸及其拆方可显著改善溃疡性结肠炎大鼠的一般行为表现及结肠组织炎症程度。②乌梅丸及其拆方对溃疡性结肠炎有明显的治疗作用,其作用机制包括维持细胞因子网络平衡；抑制炎性介质的释放,抗氧化损伤；抑制TLR4/NF-κB信号通路的传导；促进胃肠功能的恢复和镇痛。③乌梅丸不同属性药物从不同方面对溃疡性结肠炎发挥治疗作用。寒凉组药物在降低结肠组织TNF-α、IL-1、MPO含量等方面作用突出；温热组药物在降低结肠组织PGE2、PAF含量,升高IL-10含量以及促进胃肠功能恢复和镇痛方面作用显著；补益组药物升高血清及结肠组织SOD活性作用明显；寒热不同药性药物均能降低血清白细胞计数,结肠组织TNF-a、lL-1含量,抑制TLR4/NF-κB信号通路的传导,寒热配伍后产生了显著的协同增效作用,寒热配伍能抑制单纯应用寒凉或温热药所产生的不利作用,寒热配伍后体现了中医药多靶点的治疗优势。
Objective:Observe the influence on Wumei Pill and its Subdivisions about rats of ulcerative colitis (UC) in respects of histocytology, inflammatory mediator and the signal pathway of TLR4/NF-κB, and analysis the targets and mechanism of action about the treatment effects of Wumei Pill and its Subdivisions and the effect on compatibility of both cold and heat in Wumei Pill on treat ulcerative colitis (UC).Discuss the mechanism of action about different compatibility of both cold and heat, and then disclose the synergy or restricting effects on heat and cold drug of different attributed groups.
Methods:①Select male SD rats and establish ulcerative colitis model. After8hours, all the rats except blank group were given of Wumei Pill or its Subdivisions. After12days, observe rats' gastrointestinal function and pathological morphology change of colon. Test TNF-α、PGE2、IL-1、IL-10、MPO、PAF contents in ELISA method and TLR4、MYD88、NF-KBmRNA expressions of colon tissue of rats in RT-PCR method and the SOD of colon tissue and serum in xanthine oxidase method.②Select Kunming mice All the groups'mice were given of Wumei Pill or its Subdivisions for5days. After30minutes, each mouse was given0.2ml0.6%Acetic acid by intraperitoneal injection and then observer the times of twist body reaction after30minutes. Finally, record the time of first appearing twist body reaction, and then calculate the average times of twist body and analgesic percentage.
Result:①General behavior:The rats'spirit, diet, fur color and weight were signify-cantly improved Wumei Pill group and cold and heat application group.②Patholo-gical observation:The model group rats'colonic mucosal surface is rough, and there are a lot of infiltrations of inflammatory cells, glandular atrophy, disordered, goblet cell morphology change, a crypt abscess formation, visible ulcers or mucosal defect with a large area. Some rats even damage the sub mucosa, and manifested as sub-mucosa massive inflammatory cell infiltration. After treatment, the pathological changes were eased of Wumei Pill group and cold and heat application group, and other groups are still visible in the infiltration of inflammatory cells and other inflam-matory manifesttations.③Serum white blood cell count, IL-1, TNF-α and MPO content of colonic tissue:Compared with blank group, the serum white blood cell count, IL-1, TNF-a and MPO content were significantly elevated of model group rats while it decreased obviously of Wumei Pill group, cold and heat application group, heat group, cold and tonic group (P<0.01).Compared with Wumei Pill group, they were significant different of cold and heat application group,cold group, heat group and tonic group (P<0.01).④SOD activity of colonic tissue and serum, PGE2content of colonic tissue:Compared with blank group, the PGE2content of colonic tissue were signi-ficantly increased and the IL-10content, SOD activity of colonic tissue were signi-ficantly decreased of model group rats while they were decreased obviously of Wumei Pill group, cold and heat application group, heat group and tonic group (P<0.01).⑤PAF content of colonic tissue:Compared with blank group, the PAF content of colonic tissue were significantly increased of model group rats while it is decreased of Wumei Pill group, cold and heat application group, heat group and cold group (P<0.01or P<0.05). Compared with Wumei Pill group, the PAF content of colonic tissue were different of cold group(P<0.01).⑥TLR4、MYD88.NF-KBmRNA expression of colonic tissue:Compared with blank group, the TLR4、MYD88、 NF-icBmRNA expression of colonic tissue were significantly enhanced of model group rats while it is dncreased of Wumei Pill group, cold and heat application group, heat group and cold group (P<0.01or P<0.05).⑦The retention rate in the stomach raised and the small intestine motional rate:Compared with blank group, the retention rate in the stomach was significantly increased and the small intestine motional rate was significantly decreased of model group rats while the retention rate in the stomach was significantly increased and the small intestine motional rate was significantly decreased of obviously of Wumei Pill group, cold and heat application group and heat group (P<0.01),and the retention rate in the stomach was significantly decreased and the small intestine motional rate was significantly increased of astringent group.⑧The time of first appearing twist body reaction and the average times of twist body:Compared with model group, the time of first appearing twist body reaction prolonged and the average times of twist body were significantly decreased of Wumei Pill group, cold and heat application group and heat group (P<0.01)
Conclusion:①Wumei Pill and its Subdivisions can improve the ulcerative colitis rat's General behavior and reduce the inflammation degree of rats'colon tissue significantly.②Wumei Pill and its Subdivisions have obvious therapeutic effect on ulcerative colitis. The mechanisms of action include the maintenance of cytokine network equilibrium, inhibition of inflammatory mediator release and antioxidative damage, inhibition of TLR4/NF-κB pathway conduction and promoting the recovery of gastrointestinal function and analgesia.③The different properties drug of Wumei Pill plays a therapeutic role from different aspects on ulcerative colitis. Cold group of drugs play an important part on reducing the TNF-α, IL-1and MPO of colonic tissue; Heat group of drugs play an important part on reducing the PGE2, PAF content of colonic tissue, increasing the IL-10content of colonic tissue and promoting the recovery of gastrointestinal function and analgesia; Tonic group of drugs play an important part on increasing the SOD activity of colonic tissue and serum; Cold and heat of different drugs can reduce serum white blood cell count. TNF-α and IL-1content of colonic tissue, inhibit TLR4/NF-κB pathway conduction. After compatibility of cold and heat drugs, the synergistic effect significant was reinforced. Compatibility of cold and heat drugs can inhibit the adverse effect of cold or warm drugs and embody the Chinese medicine targeted therapeutic advantage.
方法：①雄性SD大鼠,采用大承气汤合TNBS/乙醇复制寒热错杂型溃疡性结肠炎动物模型,8h后给予乌梅丸拆方灌胃,12d后处死大鼠,检测胃肠功能、血常规,光镜观察结肠组织病理学变化,EL1SA法检测结肠组织TNF-α、PGE2、IL-1、IL-10、MPO、PAF含量；RT-PCR检测结肠组织TLR4、MYD88、NF-KBmRNA的表达,黄嘌呤氧化酶法测定结肠组织和血清SOD活性。②雌雄各半昆明小鼠,各组给予乌梅丸拆方灌胃给药,30min后,腹腔均注射0.6%乙酸溶液0.2ml/只,记录注射后30min内出现的扭体反应次数,最早扭体出现时间,计算平均扭体次数、镇痛率,连续观察5d。
结果：①一般行为表现：全方组、寒热并用组的精神状态、饮食、皮毛色泽、体重等情况较模型组明显改善,且全方组、寒热并用组优于其余各组。②病理形态学观察：模型组大鼠结肠粘膜表面起伏不平,可见大量炎性细胞浸润,腺体萎缩,排列紊乱,杯状细胞形态改变,有隐窝脓肿形成,可见溃疡面或粘膜大面积缺损,严重的甚至损害粘膜下层,表现为粘膜下层大量炎性细胞浸润。给药治疗后,全方组及寒热并用组上述病理改变明显减轻,其余各组仍可见炎性细胞浸润等炎症表现。③血清白细胞计数,结肠组织IL-1、TNF-α、MPO含量：与空白组比较,血清白细胞计数,结肠组织IL-1、TNF-a、MPO含量显著升高,全方组、寒热并用组、温热组、寒凉组和补益组明显降低(P<0.01)；与全方组比较,寒热并用组、寒凉组、温热组和补益组有显著性差异(P<0.01)。④血清SOD和结肠组织PGE、IL-10含量、SOD活性：与空白组比较,模型组大鼠结肠组织PGE2含量升高,IL-10含量和SOD活性降低,全方组、寒热并用组、温热组和补益组大鼠结肠组织PGE2显著降低,IL-10含量和SOD活性显著升高(P<0.01),寒凉组、收敛组无差异(P>0.05)。⑤结肠组织PAF含量：与空白组比较,模型组大鼠结肠组织PAF含量显著升高,全方组、寒热并用组、温热组显著降低(P<0.01),寒凉组降低(P<0.05)；与全方组比较,寒凉组有显著性差异(P<0.01)。⑥大鼠结肠组织TLR4、MYD88、NF-κBmRNA表达：与空白组比较,模型组大鼠结肠组织TLR4、MYD88、NF-κBmRNA表达显著增强(P<0.01)。全方组和寒热并用组表达明显降低(P<0.01),温热组和寒凉组表达降低(P<0.05)；与全方组比较,寒热并用组无差异(P>0.05)。⑦大鼠胃残留率和小肠推进率：与空白组比较,模型组大鼠胃残留率明显升高,小肠推进率降低(P<0.01)。全方组、寒热并用组、温热组胃残留率降低,小肠推进率升高,有显著性差异(P<0.01),收敛组胃残留率升高,小肠推进率降低(P<0.01)；与全方组比较,寒热并用组和温热组无差异(P>0.05)。⑧最早扭体时间,平均扭体次数：与模型组比较,全方组、寒热并用组和温热组最早扭体时间延长,平均扭体次数降低(P<0.01),收敛组和补益组平均扭体次数降低(P<0.01)；寒凉组无差异(P>0.05)；与全方组比较,寒热并用组和温热组无差异(P>0.05)。
结论：①乌梅丸及其拆方可显著改善溃疡性结肠炎大鼠的一般行为表现及结肠组织炎症程度。②乌梅丸及其拆方对溃疡性结肠炎有明显的治疗作用,其作用机制包括维持细胞因子网络平衡；抑制炎性介质的释放,抗氧化损伤；抑制TLR4/NF-κB信号通路的传导；促进胃肠功能的恢复和镇痛。③乌梅丸不同属性药物从不同方面对溃疡性结肠炎发挥治疗作用。寒凉组药物在降低结肠组织TNF-α、IL-1、MPO含量等方面作用突出；温热组药物在降低结肠组织PGE2、PAF含量,升高IL-10含量以及促进胃肠功能恢复和镇痛方面作用显著；补益组药物升高血清及结肠组织SOD活性作用明显；寒热不同药性药物均能降低血清白细胞计数,结肠组织TNF-a、lL-1含量,抑制TLR4/NF-κB信号通路的传导,寒热配伍后产生了显著的协同增效作用,寒热配伍能抑制单纯应用寒凉或温热药所产生的不利作用,寒热配伍后体现了中医药多靶点的治疗优势。
Objective:Observe the influence on Wumei Pill and its Subdivisions about rats of ulcerative colitis (UC) in respects of histocytology, inflammatory mediator and the signal pathway of TLR4/NF-κB, and analysis the targets and mechanism of action about the treatment effects of Wumei Pill and its Subdivisions and the effect on compatibility of both cold and heat in Wumei Pill on treat ulcerative colitis (UC).Discuss the mechanism of action about different compatibility of both cold and heat, and then disclose the synergy or restricting effects on heat and cold drug of different attributed groups.
Methods:①Select male SD rats and establish ulcerative colitis model. After8hours, all the rats except blank group were given of Wumei Pill or its Subdivisions. After12days, observe rats' gastrointestinal function and pathological morphology change of colon. Test TNF-α、PGE2、IL-1、IL-10、MPO、PAF contents in ELISA method and TLR4、MYD88、NF-KBmRNA expressions of colon tissue of rats in RT-PCR method and the SOD of colon tissue and serum in xanthine oxidase method.②Select Kunming mice All the groups'mice were given of Wumei Pill or its Subdivisions for5days. After30minutes, each mouse was given0.2ml0.6%Acetic acid by intraperitoneal injection and then observer the times of twist body reaction after30minutes. Finally, record the time of first appearing twist body reaction, and then calculate the average times of twist body and analgesic percentage.
Result:①General behavior:The rats'spirit, diet, fur color and weight were signify-cantly improved Wumei Pill group and cold and heat application group.②Patholo-gical observation:The model group rats'colonic mucosal surface is rough, and there are a lot of infiltrations of inflammatory cells, glandular atrophy, disordered, goblet cell morphology change, a crypt abscess formation, visible ulcers or mucosal defect with a large area. Some rats even damage the sub mucosa, and manifested as sub-mucosa massive inflammatory cell infiltration. After treatment, the pathological changes were eased of Wumei Pill group and cold and heat application group, and other groups are still visible in the infiltration of inflammatory cells and other inflam-matory manifesttations.③Serum white blood cell count, IL-1, TNF-α and MPO content of colonic tissue:Compared with blank group, the serum white blood cell count, IL-1, TNF-a and MPO content were significantly elevated of model group rats while it decreased obviously of Wumei Pill group, cold and heat application group, heat group, cold and tonic group (P<0.01).Compared with Wumei Pill group, they were significant different of cold and heat application group,cold group, heat group and tonic group (P<0.01).④SOD activity of colonic tissue and serum, PGE2content of colonic tissue:Compared with blank group, the PGE2content of colonic tissue were signi-ficantly increased and the IL-10content, SOD activity of colonic tissue were signi-ficantly decreased of model group rats while they were decreased obviously of Wumei Pill group, cold and heat application group, heat group and tonic group (P<0.01).⑤PAF content of colonic tissue:Compared with blank group, the PAF content of colonic tissue were significantly increased of model group rats while it is decreased of Wumei Pill group, cold and heat application group, heat group and cold group (P<0.01or P<0.05). Compared with Wumei Pill group, the PAF content of colonic tissue were different of cold group(P<0.01).⑥TLR4、MYD88.NF-KBmRNA expression of colonic tissue:Compared with blank group, the TLR4、MYD88、 NF-icBmRNA expression of colonic tissue were significantly enhanced of model group rats while it is dncreased of Wumei Pill group, cold and heat application group, heat group and cold group (P<0.01or P<0.05).⑦The retention rate in the stomach raised and the small intestine motional rate:Compared with blank group, the retention rate in the stomach was significantly increased and the small intestine motional rate was significantly decreased of model group rats while the retention rate in the stomach was significantly increased and the small intestine motional rate was significantly decreased of obviously of Wumei Pill group, cold and heat application group and heat group (P<0.01),and the retention rate in the stomach was significantly decreased and the small intestine motional rate was significantly increased of astringent group.⑧The time of first appearing twist body reaction and the average times of twist body:Compared with model group, the time of first appearing twist body reaction prolonged and the average times of twist body were significantly decreased of Wumei Pill group, cold and heat application group and heat group (P<0.01)
Conclusion:①Wumei Pill and its Subdivisions can improve the ulcerative colitis rat's General behavior and reduce the inflammation degree of rats'colon tissue significantly.②Wumei Pill and its Subdivisions have obvious therapeutic effect on ulcerative colitis. The mechanisms of action include the maintenance of cytokine network equilibrium, inhibition of inflammatory mediator release and antioxidative damage, inhibition of TLR4/NF-κB pathway conduction and promoting the recovery of gastrointestinal function and analgesia.③The different properties drug of Wumei Pill plays a therapeutic role from different aspects on ulcerative colitis. Cold group of drugs play an important part on reducing the TNF-α, IL-1and MPO of colonic tissue; Heat group of drugs play an important part on reducing the PGE2, PAF content of colonic tissue, increasing the IL-10content of colonic tissue and promoting the recovery of gastrointestinal function and analgesia; Tonic group of drugs play an important part on increasing the SOD activity of colonic tissue and serum; Cold and heat of different drugs can reduce serum white blood cell count. TNF-α and IL-1content of colonic tissue, inhibit TLR4/NF-κB pathway conduction. After compatibility of cold and heat drugs, the synergistic effect significant was reinforced. Compatibility of cold and heat drugs can inhibit the adverse effect of cold or warm drugs and embody the Chinese medicine targeted therapeutic advantage.
引文
[1]欧阳钦,Rakesh Tandon,K L Goh,等.亚太地区炎症性肠病处理共识意见(一)[J].胃肠病学,2006,,11(4)：233-238
[2]中华医学会消化病学分会炎症性肠病协作组.对我国炎症性肠病诊断治疗规范的共识意见[J].胃肠病学,2007,12(8)：488-495
[3]范恒,段霄云,庄雄等.乌梅丸对溃疡性结肠炎大鼠结肠组织NF-κ3 P65的影响[J].世界华人消化杂志,2008,16(8)896-899
[4]熊俊,董文军.乌梅丸及其加减方治疗溃疡性结肠炎临床随机对照试验的系统评价[J].吉林中医药,2008,28(4)：296-299
[5]卢贺起,张玲.乌梅丸治疗溃疡性结肠炎方证相应的实验研究[J].中国中医基础医学杂志.2010,16(8)：677-679
[6]刚峰,卜平.白头翁加味汤调节溃疡性结肠炎大鼠血清白介素-4和肠黏膜环氧合酶-2的研究[J].中国实验方剂学杂志,2009,15(12)：84-86
[7]冯娟,刘莉.半夏泻心汤抑制OMH/OSS诱导的结肠炎相关性结肠癌的发生[J].世界华人消化杂志,2007,15(14)：1609-1614
[8]殷胜骏.韩涛,薛新丽.溃疡性结肠炎临床用药聚类分析[J].中国实验方剂学杂志,2008,14(6)：77-79
[9]邓中甲方剂学[M].北京：中国中医药出版社,2002：345
[10]邓中甲方剂学[M].北京：中国中医药出版社,2002：59
[11]陈奇.中药药效的研究思路与方法[M].北京：人民卫生出版社.2005：444
[12]Min Zhang, Yin Long,Yang Sun.Evidence for the complementary and synergistic effects of the three-alkaloid combination regimen containing berberine, hypaconi-tine and skimmianine on the ulcerative colitis rats induced by trinitro benzene-sulfonic acid[J].European Journal of Pharmacology 651 (2011) 187-196
[13]刘莉,梅其炳.大黄多糖对TNBS诱导大鼠结肠炎的治疗作用[J].中国中药杂志,2003,28(3)：246-249
[14]刘莉,梅其炳地塞米松对TNBS诱导的大鼠实验性结肠炎的治疗作用[J].第三军医大学学报,2002,24(7)：793-794
[15]高英茂李和组织学与胚胎学[M].人民卫生出版社2010.872
[16]Papadakis CA, Targan SA. Tumor necrosis factor:biology and therapeutic inhibitors [J]. Gastroenterology,2000.119:1148-1157.
[17]BlamME, Stein RBS. Lichtenstein GR. Integrating anti-tumornecrosis factor therapy in infla-mematory bowel disease. Current and future perspectives [J]. Am J Gastroentero,1 2001,96:1977-1997
[18]Kerawala M, Ambler JE, Lee PYC, et al.In vitro activity of gemifloxacin (SB-265805) compared to eleven other antimicrobial agents againstStreptococcal isolates, excluding Streptococcus pneumoniae[J].Eur J ClinMicrobiol Infect Dis,2001,20(4):271-275.
[19]蒋志坚,曹文涛.溃疡性结肠炎患者血清TNF-α、IL-1β的临床意义[J].中国现代医生2009,47(16)：63
[20]Ali T, Yun L, Rubin DT.Risk of post-operative complications associated with anti-TNF therapy in inflammatory bowel disease[J]. World J Gastroenterol.2012 Jan 21:18(3):197-204.
[21]段进粮,聂玉强.大鼠溃疡性结肠炎模型血清TNF-α和IL-10的观察[J].广州医学院院报2008,3：14-16
[22]郑礼,王淑仙,崔德玉.介绍一种简便的炎症性肠炎疾病的评价方法[J].中国药理学报,1996；]2(5)：468-469
[23]郑礼,高振强.大鼠溃疡性结肠炎模型的实验研究[J].中国药理学通报1998,14(4)：370-372
[24]DongWG, Liu SP, Yu BP, et a.l Ameliorative effects of sodium fer-ulate on experimental colitis and theirmechanism in rats[J].World J Gastroentero.l 2003.9(11):2533.
[25]BlazovicsA, HagymasiK, PronaiL. Cytokines, prostaglandins, nutri-tive and non-nuitritive factors in inflammatory bowel diseases[J].OrvHeti,l 2004,145(50):2523.
[26]Degagne E, Grbic DM, Dupuis AA, et.al P2Y2 receptor transcription is increased by NF-kappa B and stimulates cyclooxygenase-2 expression and PGE2 released by intestinal epithelial cells[J]. Immunol.2009 Oct 1;183(7):4521-4529.
[27]李玉生.溃疡性结肠炎患者血清PGE2、PAF水平变化及其临床意义[J].实用临床医药杂志2010,14(11)：17-19
[28]崔云华,周爽,吴焕淦.从细胞凋亡角度验证隔药灸对溃疡性结肠炎大鼠环氧合酶2及前列腺素E2的调节作用[J].中国组织工程研究与临床康复,2008,,12(24)：4680-4684
[29]Rodriguez-Perlvarez ML, Sanchez VG,et.alRole of serum cytokine profile in ulcerative colitis assessment[J].Inflamm Bowel Dis.2012 Jan 11. doi:10.1002/ibd.22865
[30]高伟,司雁菱,吴瑜.溃疡性结肠炎患者结肠黏膜中IL-10、IL-13表达变化及意义[J].山东医药2010,50(11)：80
[31]周毅,邓虹珠,朱学敏.苦豆子总碱对大鼠溃疡性结肠炎细胞因子IL-10表达的影响[J].国际消化病杂志,2007,27(6)：465-467
[32]陈友岱,周总光.血小板活化因子与局部微循环障碍[J].中国微循环,2001,5(3)：241-243.
[33]KoHM, SeoKH,Han SJ.Nuclear factorkappa B dependency ofplatelet-activating factor-induce dangiogenesis[J]. CancerRes,2002,62:1809-1814.
[34]李振吉,张先恩,苏钢强.973计划中医理论基础研究专项[M].中国中医药出版社2011：144-145
[35]Rezaie A, Parker RD, Rezaie A. Oxidative stress and pathogenesis of inflammatory bowel disease:an epiphenomenon or the cause? [J].Dig Dis Sci.2007;52:2015-21.
[36]Suzuki Y, Matsumoto T, Okamoto S, A lecithinized superoxide dismutase (PC-SOD) improves ulcerative colitis[J]. Colorectal Dis.2008 Nov;10(9):931-4. Epub 2008 Feb 21.
[37]崔莉,胡晋红.化学诱导型结肠炎动物模型的研究进展[J].中国药理学通报,2005,21(5)：522-526.
[38]马建华,郑绘霞,赵玉泽.肠必清栓对UC模型大鼠肠黏膜内IL-1β、TNF-α及SOD的影响[J].中国医药导报,2010,7(2)：6-8
[39]Yao J, Wang JY, Liu L.Anti-oxidant effects of resveratrol on mice with DSS-induced ulcerative colitis[J].Arch Med Res.2010 May;41(4):288-294.
[40]陈胜,邹开芳,杨天.Toll样受体2、4、9在大鼠结肠炎模型结肠组织中的表达及意义[J].胃肠病学,2007,12(6)：339-343.
[41]张可.NF-κB与炎症性肠病[J].国外医学·消化系疾病分册,2003,23(2)：94-96
[42]TitusAR, AlexCC, CharlesAP. Neutrophil transepithelial migration:role of toll-like receptors inmucosal inflammation [J]. Mem InstOswaldo Cruz,2005,100(Suppll):191-198
[43]Li Z,Zhang de K,Yi WQ,Ouyang Q,Chen YQ,Gan HT.NF-kappa B p65 anti-sense oligo nucleotides may serve as a novel molecular approach for treatment of patients with ulcerative colitis[J].Arch Med Res 2008;39:729-734
[44]梁海清,李俊玲.NF-κB在UC中的作用[J].国际消化病杂志,2008,28(1)：40.
[45]陈吉,高美丽,白晓茹,等.核因子-KB和细胞因子在UC中的表达及其意义[J].世界华人消化杂志,2009,17(2)：209.
[46]Sivaram G, Tiwari SK, Bardia A, et.al Macrophage migration inhibitory factor, Toll-like receptor 4, and CD14polymorphisms with altered expression levels in patients with ulcerative colitis[J].Hum Immunol.2012 Feb;73(2):201-205.
[47]李佃贵,戎士玲,张江华,等.糖尿病大鼠胃肠功能障碍与胃动素、胆囊收缩素、生长激素相关性研究[J].中国糖尿病杂志,2008,16(9)：571-572.
[48]袁静.中医药对胃肠动力异常研究进展[J].中国中医急症,2011,20(3)：440-441
[49]陈奇.中药药理研究方法学[M].2版.北京：人民卫生出版社,2006：366-368.
[50]柳瑞凤194例溃疡性结肠炎临床分析[J].宜春学院学报,2010,32(8)：62-63
[51]梁丽娜,刘丽娜.溃疡性结肠炎140例临床分析[J].大连医科大学学报.2010,32(5)531-534
[52]谭英乌梅丸加味治疗慢性非特异性溃疡性结肠炎48例总结[J].湖南中医杂志,2008,24(6)：7-8
[53]李振吉,于文明,张先恩,等.973计划中医理论基础研究专项实施概要[M].北京,中国中医药出版社,2011：85
[54]周天羽,张扬,王俊江.免疫复合法建立大鼠溃疡性结肠炎模型的研究[J].中医药学报2005.33(6)：23-24
[55]谷松,关庆增,明彩荣.溃疡性结肠炎肝郁大鼠模型的实验研究[J].辽宁中医药杂志2005,32(11)：1210
[56]朱代华,张兴明,郭丹.二硝基苯磺酸诱导的鼠溃疡性结肠炎动物模型[J].重庆医科大学学报,2004,29(4)：486-488
[57]王显飞,陈烨,陈村龙,等.急性结肠炎慢性化小鼠模型的建立[J].胃肠病学,2008,13(3)：167-169
[58]段征,汪维伟.溃疡性结肠炎大鼠模型研究现况[J].重庆医学,2007,第36(7)：661-662
[59]黄永年,张元德,邢玉馥.大鼠溃疡性结肠炎模型的建立与观察[J].中华病理学杂志,1995,24(6)：392
[60]白玉宾气血水相关理论和溃疡性结肠炎发病的相关性[J].辽宁中医杂志,2011,38(4)613-615
[61]刘大铭,王新月难治性溃疡性结肠炎中医病因病机探讨[J].中医杂志,2011,52(24)：2156-2157
[62]杜健鹏陈泽涛益气活血法改善微循环的实验研究[J].中国实验方剂学杂志,2006；12(9)：31-35
[63]周永学.中药寒热并用在方剂配伍中的应用[J].中华中医药杂志,2010,25(10)1543
[64]严石林,陶怡,邓瑞镇,等.从《伤寒论》探讨寒热错杂证候辨治[J].中华中医药杂志,2011,26(10)2203
[65]Chen Y, Wong RW, Seneviratne CJ, The antimicrobial efficacy of Fructus mume extract on orthodontic bracket:a monospecies-biofilm model study in vitro. Arch Oral Biol.2011 Jan;56(1): 16-21. Epub 2010 Sep 22.
[66]Kwon HA, Kwon YJ, Kwon DY, Lee JH.Evaluation of antibacterial effects of a combination of Coptidis Rhizoma, Mume Fructus. and Schizandrae Fructus against Salmonella. Int J Food Microbiol.2008 Sep 30; 127(1-2):180-3. Epub 2008 Jun 29.
[67]Round JL, Mazmanian SK. The gut microbiota shapes intestinal immune responses during health and disease Nat Rev Immunol,2009,9(5):313-323
[1]郭锦艳,陈卫.1998—2009年肠道非肿瘤性疾病住院患者临床特点调查分析[J].中国全科医学,2011.14：1334-1336
[2]Rodriguez-Perlvarez ML. Sanchez VG,et.al Role of serum cytokine profile in ulcerative colitis assessment[J].Inflamm Bowel Dis.2012 Jan 11. doi:10.1002/ibd.22865
[3]张晓博.IL-1β、IL-13、TNF-α在溃疡性结肠炎患者血清中的表达[J].河北医药2009,31(24)：3394
[4]魏思忱.IL-10在溃疡性结肠炎患者血清中的表达及意义[J].河北医药2010,32(5)559
[5]王觅柱.溃疡性结肠炎患者血清IL-lβ、TNF-α和lL-10的表达及其意义[J].国际消化病杂志,2009,29(5)：362
[6]任保从.溃疡性结肠炎患者血清IL-6、IL-8、TNF-α水平变化及意义[J].山东医药.2010,50(26)：57
[7]张晓博.溃疡性结肠炎患者血清和结肠组织白细胞介素8和白细胞介素10的表达[J].临床荟萃,2010.25(3)：210
[8]Tak PP, Firestein GS. NF-κB:a key role in inflammatory diseases[J].J Clin Invest.2001,107: 7-11.
[9]Sivaram G. Tiwari SK, Bardia A. et.al Macrophage migration inhibitory factor, Toll-like receptor 4, and CD 14 polymorphisms with altered expression levels in patients with ulcerative colitis[J].Hum Immunol.2012 Feb;73(2):201-5.
[10]李军华NF-κB、iNOS在大鼠实验性结肠炎肠组织的表达及意义[J].胃肠病学和肝病学杂志,2003,12(5)：436-439
[11|Thomas S. Baumgart DC. Targeting leukocyte migration and adhesion in Crohn's disease and ulccrative colitis[J].lnflammopharmacology.2012 Feb;20(1):1-18.
[12]范恒.理肠四方对溃疡性结肠炎大鼠血液粘附分子C044、C054的影响[J].世界华人消化杂志,2005,13(3)：398-340
[13]Sklyarov AY. Panasyuk NB, Fomenko IS. Role of nitric oxide-synthase and cyclooxygenase/lipooxygenase systems in development of experimental ulcerative colitis[J].J Physiol Pharmacol.2011 Feb:62(1):65-73.
[14]徐萍,周小江.溃疡性结肠炎组织中环氧合酶-2与一氧化氮合酶的表达及意义[J].中华消 化内镜杂志2003,20：98-399
[15]陈香宇,段芳龄,马军,等.5-氨基水杨酸对实验性结肠炎大鼠结肠粘膜NO水平的影响[J].郑州大学学报(医学版)2003,38(1)：37-39
[16]Wardle TD, Hall L, Turnberg LA. Platelet activating factor:release from colonic mucosa in patients with ulcerative colitis and its effect on colonic secretion. Gut[J].1996 Mar;38(3):355-61.
[17]Degagne E, Grbic DM, Dupuis AA, et.al P2Y2 receptor transcription is increased by NF-kappa B and stimulates cyclooxygenase-2 expression and PGE2 released by intestinal epithelial cells[J].Immunol.2009 Oct 1;183(7):4521-9. Epub 2009 Sep 4.
[18]沈琳,陈丽云,李洁.严世芸辨治溃疡性结肠炎验案1则[J].上海中医药杂志2010,44(11)：30-31
[19]黄丽,张士卿.张士卿教授治疗溃疡性结肠炎经验[J].甘肃中医学院学报,2009,26(2)：2
[20]章一凡,任光荣.任光荣治疗溃疡性结肠炎经验[J].中国现代医生,,2010,48(7)：43
[21]霍传彬.刘学勤主任医师治疗溃疡性结肠炎经验浅析[J].中医学报2009,24(5)：67-68
[22]中国中西医结合学会消化系统疾病专业委员会,2010’西昌溃疡性结肠炎中西医结合诊疗指南[J].中国中西医结合消化杂志.2011,19(1)：61-63
[23]中华中医药学会脾胃病分会.溃疡性结肠炎中医诊疗共识(2009)[J].中国中西医结合杂志,2010,30(5)：527-532
[24]郑筱萸.中药新药临床研究指导原则[M].北京：中国医药科技出版社,2002：129-134.
[25]中华中医药学会.中医内科常见病诊疗指南西医疾病部分[M].北京：中国中医药出版社,2008：107-110.
[26]国家中医药管理局.中医病证诊断疗效标准[M].南京：南京大学出版社,1994：9-10.
[27]陈爱霞,冯江雪,张磊.安肠止泻汤治疗溃疡性结肠炎42例[J].新中医2009,4l(2)：73
[28]李晟,林振文,朱子奇.白术芍药散联合传统方法治疗溃疡性结肠炎87例[J].海峡药学2009,21(8)：130
[29]刘道喜.白头翁汤加味治疗溃疡性结肠炎87例[J].江西中医药2011,10(8)：16
[30]周莺歌.半夏泻心汤治疗慢性溃疡性结肠炎58例[J].中国中医药2010,8(15)：
[31]陈小刚,曲晓璐.半夏泻心汤加味治疗慢性非特异性溃疡性结肠炎60例临床观察[J].湖南中医学院学报,2000,20(2)：49-50
[32]李志伟.补止清活汤治疗溃疡性结肠炎65例[J].中国中医急症,2010,19(3)：507
[33]胡宏中.大黄牡丹汤加减治疗溃疡性结肠炎34例[J].辽宁中医杂志第2000,27(4)：171
[34]徐彦龙,杜元灏,徐秀梅.隔药铺灸治疗慢性非特异性溃疡性结肠炎[J].中国针灸2010,30(4)：289-299
[35]任天飞.活血生肌汤灌肠治疗溃疡性结肠炎31例[J].浙江中医杂志,2000,35(7)：286
[36]鲁龙生.芍药汤治疗湿热内蕴型溃疡性结肠炎30例[J].中国中医药,2010,8(19)：11
[37]周君丰,胡敏霞.四君子汤配合痛泻要方治疗溃疡性结肠炎30例[J].陕西中医,2010,31(5)：539-540
[38]吴春江,赵双梅.痛泻要方加减治疗慢性非特异性溃疡性结肠炎50例[J].山东中医杂志,2010,29(3)：158-159
[39]樊金玲.乌梅丸合芍药甘草汤治疗慢性非特异性溃疡性结肠炎30例[J].广西中医药,19992：17
[40]谭英.乌梅丸加味治疗慢性非特异性溃疡性结肠炎48例总结[J].湖南中医杂2008,24(6)：7-8
[41]黄耀全,王志强.针灸结合四君子合剂治疗溃疡性结肠炎40例[J].广西中医药,2008,31(6)15-16
[42]梁丽.p2AR、β-arrestin2、NF-κBp65在溃疡性结肠的表达及乌梅丸的干预作用[J].世界华人消化杂志,2010,18(16)：1650-1655
[43]明彩荣,张丽红,王守岩.乌梅丸治疗大鼠溃疡性结肠炎的实脸研究[J].中国中医药科技,2007,14(1)：51
[44]殷刚峰,卜平,朱海航.白头翁加味汤调节溃疡性结肠炎大鼠血清白介素-4和肠黏膜环氧合酶-2的研究[J].中国实验方剂学杂志,2009,15(12)：84-86
[45]秦建梅,程小丽,安方玉.半夏泻心汤合四神丸加减方对溃疡性结肠炎大鼠NO、NOS及TNF-a的影响[J].甘肃中医,2010,23(6)：29-31
[46]卢健,马骥,王丽娜,等.四逆散对实验性UC大鼠血TNF-a和lL-10的影响[J].陕西中医学院学报,2010,33(6)：61-62
[47]胡旭光,利红宇.痛泻要方对肝郁脾虚型溃疡性结肠炎动物模型的治疗作用[J].广东药学院学报2004,20(1)：40-42
[48]范恒,邱明义,户菲菲,等.理肠四方对溃疡性结肠炎大鼠血液粘附分子CD44、CD54的影响[J].世界华人消化杂志,2005,13(3)：397-400
[49]吴焕淦,黄臻,刘慧荣,等.针灸对大鼠溃疡性结肠炎结肠上皮细胞凋亡影响的实验研究[J].中国针灸,2005,25(2)：119-122
[50]姚茹冰,邱明义,蔡辉,等.乌梅丸对溃疡性结肠炎大鼠病变结肠粘膜局部肿瘤坏死因子α、白介素—8及白介素—10的影响[J].中医杂志,2002,43(12)：935-936
[51]余欣邱明义,胡继鹰,等.乌梅丸对溃疡性结肠炎大鼠肠组织核转录因子-κB及细胞间黏附分子1的影响[J].中国中西医结合消化杂志,2008,16(3)：172
[52]姚茹冰,邱明义,胡兵,等.乌梅丸对溃疡性结肠炎大鼠结肠粘膜形态学的影响[J].广州中医药大学学报2003,20(1)：59-62
[53]范恒,段雪云,庄雄,等.乌梅丸对溃疡性结肠炎大鼠结肠组织NF-KBp65的影响[J].世界华人消化杂志2008,16(8)：896-899
[54]范恒,邱明义,梅家俊,等.乌梅丸对溃疡性结肠炎大鼠组织细胞因子的干预效应[J].中国临床康复,2006,10(7)：87-89
[55]姚民武,李保良,黄水清.乌梅丸对溃疡性结肠炎患者血清TNF—a、IL—6及IL—8含量的影响[J].医学信息,2010,8：2188-2189
[56]陈林,陈鸿平,刘友平.乌梅不同部位药理作用研究[J].中国药房,2007,18(27)：2089-2090
[57]刘友平,陈鸿平,万德光.乌梅的研究进展[J].中药材,2004,27(6)：459-461
[58]李仲兴,王秀华,张立志,等.应用M--H琼脂进行五倍子等5种中药对28株肠球菌的体外抗菌活性观察[J].中草药,2001,32(12)：1101
[59]张明发,沈雅琴,朱自平,等.干姜温中止痛作用的研究[J].两北药学杂志,1996,11(4)：186
[60]王梦,钱红美,苏简单.干姜乙醇提取物解热镇痛及体外抑菌作用研究[J].中药新药与临床药理,2003,14(5)：299.
[61]中药药理学沈映君人民卫生出版社北京2000：494-495
[62]陈玉春.人参附子与人参附子汤免疫调节作用机理初探[J].中成药1994,16(8)：30
[63]肖庆慈.肉桂赤石脂的配伍研究[J].云南中医学院学报1996,19(4)：1
[64]陈家源牙启康卢文.中药肉桂的研究概况[J].广西医学2009,31(6)：872-874
[65]朱自平.张明发.沈雅琴,等.肉桂的温中止痛药理研究[J].中国中药杂志.1993,18(9)：553-557.
[66]张明发.花椒抗脾胃虚寒证的药理作用研究[J].中药药理与临床,1994,10(2)：37
[67]欧阳杰湖,潘善庆,陈子渊.刺壳花椒提取物消炎镇痛作用的实验研究[J].中医药导报,2008,14(12)：71-73
[68]王秀杰黄连的药理研究及现代应用[J].中国药师,2003,6(6)：370
[69]李波,朱维良,陈凯先.小檗碱及其衍生物的研究进展[J].药学学报,2008,43(8)：773-787
[70]杨周平,武志军.中药黄柏的药理作用和临床应用研究[J].甘肃医药,2010,29(3)329-330
[71]张琛,赵钢.人参皂苷Rd的药理作用研究进展[J].中国新药杂志,2011,20(11)：953-957
[72]李宗友 节译.人参根中果胶多糖的细胞保护作用[J].国外医学-中医中药分册,1992,14(2)：21
[73]胡竟一,邱春燕,雷玲细辛的镇痛和抗炎作用[J].中药药理与临床,2011,27(2)：68-69
[74]程小平,吴国泰,刘峰林.当归挥发油对实验性胃肠动力障碍的作用及机制研究[J].中药药理与临床2011；27(4)54-56
[75]王瑞琼,吴国泰,任远,等.当归挥发油对兔离体胃肠平滑肌张力的影响[J].甘肃中医学院学报,2010：27(2)：12-14
[76]乐江,彭仁,孔锐,等.当归粗多糖镇痛作用的实验研究[J].中国药学杂志,2002,37(10)：746-748.
[77]许济群.方剂学[M]上海：上海科技出版社,1993
[78]李伟东,蔡宝昌.中药复方研究思路的探讨[J].中药新药与临床药理,2004,15(3)216-218
[79]韩凌,王钦茂.方剂拆方的研究进展[J].中国实验方剂学杂志,2000,6(1)：63
[80]荆鲁,王阶,花照泉,等.中药复方配伍及拆方研究概况[J].中国中药杂志,2003,28(12)：1125-1128
[8]]邓子华,邓虹珠.中药复方拆方研究概况[J].现代中西医结合杂志,2007,16(4)：563-564
[82]高晓山.中药药性论[M].北京：人民卫生出版社,1992：256
[83]王钦茂,周光友.中药复方拆方研究概况[J].安徽中医学院学报,996,15(2)：59-61.
[84]贺又舜.方剂研究的一些思考[J].湖南中医药导报,2003,9(2)：42-44.
[2]中华医学会消化病学分会炎症性肠病协作组.对我国炎症性肠病诊断治疗规范的共识意见[J].胃肠病学,2007,12(8)：488-495
[3]范恒,段霄云,庄雄等.乌梅丸对溃疡性结肠炎大鼠结肠组织NF-κ3 P65的影响[J].世界华人消化杂志,2008,16(8)896-899
[4]熊俊,董文军.乌梅丸及其加减方治疗溃疡性结肠炎临床随机对照试验的系统评价[J].吉林中医药,2008,28(4)：296-299
[5]卢贺起,张玲.乌梅丸治疗溃疡性结肠炎方证相应的实验研究[J].中国中医基础医学杂志.2010,16(8)：677-679
[6]刚峰,卜平.白头翁加味汤调节溃疡性结肠炎大鼠血清白介素-4和肠黏膜环氧合酶-2的研究[J].中国实验方剂学杂志,2009,15(12)：84-86
[7]冯娟,刘莉.半夏泻心汤抑制OMH/OSS诱导的结肠炎相关性结肠癌的发生[J].世界华人消化杂志,2007,15(14)：1609-1614
[8]殷胜骏.韩涛,薛新丽.溃疡性结肠炎临床用药聚类分析[J].中国实验方剂学杂志,2008,14(6)：77-79
[9]邓中甲方剂学[M].北京：中国中医药出版社,2002：345
[10]邓中甲方剂学[M].北京：中国中医药出版社,2002：59
[11]陈奇.中药药效的研究思路与方法[M].北京：人民卫生出版社.2005：444
[12]Min Zhang, Yin Long,Yang Sun.Evidence for the complementary and synergistic effects of the three-alkaloid combination regimen containing berberine, hypaconi-tine and skimmianine on the ulcerative colitis rats induced by trinitro benzene-sulfonic acid[J].European Journal of Pharmacology 651 (2011) 187-196
[13]刘莉,梅其炳.大黄多糖对TNBS诱导大鼠结肠炎的治疗作用[J].中国中药杂志,2003,28(3)：246-249
[14]刘莉,梅其炳地塞米松对TNBS诱导的大鼠实验性结肠炎的治疗作用[J].第三军医大学学报,2002,24(7)：793-794
[15]高英茂李和组织学与胚胎学[M].人民卫生出版社2010.872
[16]Papadakis CA, Targan SA. Tumor necrosis factor:biology and therapeutic inhibitors [J]. Gastroenterology,2000.119:1148-1157.
[17]BlamME, Stein RBS. Lichtenstein GR. Integrating anti-tumornecrosis factor therapy in infla-mematory bowel disease. Current and future perspectives [J]. Am J Gastroentero,1 2001,96:1977-1997
[18]Kerawala M, Ambler JE, Lee PYC, et al.In vitro activity of gemifloxacin (SB-265805) compared to eleven other antimicrobial agents againstStreptococcal isolates, excluding Streptococcus pneumoniae[J].Eur J ClinMicrobiol Infect Dis,2001,20(4):271-275.
[19]蒋志坚,曹文涛.溃疡性结肠炎患者血清TNF-α、IL-1β的临床意义[J].中国现代医生2009,47(16)：63
[20]Ali T, Yun L, Rubin DT.Risk of post-operative complications associated with anti-TNF therapy in inflammatory bowel disease[J]. World J Gastroenterol.2012 Jan 21:18(3):197-204.
[21]段进粮,聂玉强.大鼠溃疡性结肠炎模型血清TNF-α和IL-10的观察[J].广州医学院院报2008,3：14-16
[22]郑礼,王淑仙,崔德玉.介绍一种简便的炎症性肠炎疾病的评价方法[J].中国药理学报,1996；]2(5)：468-469
[23]郑礼,高振强.大鼠溃疡性结肠炎模型的实验研究[J].中国药理学通报1998,14(4)：370-372
[24]DongWG, Liu SP, Yu BP, et a.l Ameliorative effects of sodium fer-ulate on experimental colitis and theirmechanism in rats[J].World J Gastroentero.l 2003.9(11):2533.
[25]BlazovicsA, HagymasiK, PronaiL. Cytokines, prostaglandins, nutri-tive and non-nuitritive factors in inflammatory bowel diseases[J].OrvHeti,l 2004,145(50):2523.
[26]Degagne E, Grbic DM, Dupuis AA, et.al P2Y2 receptor transcription is increased by NF-kappa B and stimulates cyclooxygenase-2 expression and PGE2 released by intestinal epithelial cells[J]. Immunol.2009 Oct 1;183(7):4521-4529.
[27]李玉生.溃疡性结肠炎患者血清PGE2、PAF水平变化及其临床意义[J].实用临床医药杂志2010,14(11)：17-19
[28]崔云华,周爽,吴焕淦.从细胞凋亡角度验证隔药灸对溃疡性结肠炎大鼠环氧合酶2及前列腺素E2的调节作用[J].中国组织工程研究与临床康复,2008,,12(24)：4680-4684
[29]Rodriguez-Perlvarez ML, Sanchez VG,et.alRole of serum cytokine profile in ulcerative colitis assessment[J].Inflamm Bowel Dis.2012 Jan 11. doi:10.1002/ibd.22865
[30]高伟,司雁菱,吴瑜.溃疡性结肠炎患者结肠黏膜中IL-10、IL-13表达变化及意义[J].山东医药2010,50(11)：80
[31]周毅,邓虹珠,朱学敏.苦豆子总碱对大鼠溃疡性结肠炎细胞因子IL-10表达的影响[J].国际消化病杂志,2007,27(6)：465-467
[32]陈友岱,周总光.血小板活化因子与局部微循环障碍[J].中国微循环,2001,5(3)：241-243.
[33]KoHM, SeoKH,Han SJ.Nuclear factorkappa B dependency ofplatelet-activating factor-induce dangiogenesis[J]. CancerRes,2002,62:1809-1814.
[34]李振吉,张先恩,苏钢强.973计划中医理论基础研究专项[M].中国中医药出版社2011：144-145
[35]Rezaie A, Parker RD, Rezaie A. Oxidative stress and pathogenesis of inflammatory bowel disease:an epiphenomenon or the cause? [J].Dig Dis Sci.2007;52:2015-21.
[36]Suzuki Y, Matsumoto T, Okamoto S, A lecithinized superoxide dismutase (PC-SOD) improves ulcerative colitis[J]. Colorectal Dis.2008 Nov;10(9):931-4. Epub 2008 Feb 21.
[37]崔莉,胡晋红.化学诱导型结肠炎动物模型的研究进展[J].中国药理学通报,2005,21(5)：522-526.
[38]马建华,郑绘霞,赵玉泽.肠必清栓对UC模型大鼠肠黏膜内IL-1β、TNF-α及SOD的影响[J].中国医药导报,2010,7(2)：6-8
[39]Yao J, Wang JY, Liu L.Anti-oxidant effects of resveratrol on mice with DSS-induced ulcerative colitis[J].Arch Med Res.2010 May;41(4):288-294.
[40]陈胜,邹开芳,杨天.Toll样受体2、4、9在大鼠结肠炎模型结肠组织中的表达及意义[J].胃肠病学,2007,12(6)：339-343.
[41]张可.NF-κB与炎症性肠病[J].国外医学·消化系疾病分册,2003,23(2)：94-96
[42]TitusAR, AlexCC, CharlesAP. Neutrophil transepithelial migration:role of toll-like receptors inmucosal inflammation [J]. Mem InstOswaldo Cruz,2005,100(Suppll):191-198
[43]Li Z,Zhang de K,Yi WQ,Ouyang Q,Chen YQ,Gan HT.NF-kappa B p65 anti-sense oligo nucleotides may serve as a novel molecular approach for treatment of patients with ulcerative colitis[J].Arch Med Res 2008;39:729-734
[44]梁海清,李俊玲.NF-κB在UC中的作用[J].国际消化病杂志,2008,28(1)：40.
[45]陈吉,高美丽,白晓茹,等.核因子-KB和细胞因子在UC中的表达及其意义[J].世界华人消化杂志,2009,17(2)：209.
[46]Sivaram G, Tiwari SK, Bardia A, et.al Macrophage migration inhibitory factor, Toll-like receptor 4, and CD14polymorphisms with altered expression levels in patients with ulcerative colitis[J].Hum Immunol.2012 Feb;73(2):201-205.
[47]李佃贵,戎士玲,张江华,等.糖尿病大鼠胃肠功能障碍与胃动素、胆囊收缩素、生长激素相关性研究[J].中国糖尿病杂志,2008,16(9)：571-572.
[48]袁静.中医药对胃肠动力异常研究进展[J].中国中医急症,2011,20(3)：440-441
[49]陈奇.中药药理研究方法学[M].2版.北京：人民卫生出版社,2006：366-368.
[50]柳瑞凤194例溃疡性结肠炎临床分析[J].宜春学院学报,2010,32(8)：62-63
[51]梁丽娜,刘丽娜.溃疡性结肠炎140例临床分析[J].大连医科大学学报.2010,32(5)531-534
[52]谭英乌梅丸加味治疗慢性非特异性溃疡性结肠炎48例总结[J].湖南中医杂志,2008,24(6)：7-8
[53]李振吉,于文明,张先恩,等.973计划中医理论基础研究专项实施概要[M].北京,中国中医药出版社,2011：85
[54]周天羽,张扬,王俊江.免疫复合法建立大鼠溃疡性结肠炎模型的研究[J].中医药学报2005.33(6)：23-24
[55]谷松,关庆增,明彩荣.溃疡性结肠炎肝郁大鼠模型的实验研究[J].辽宁中医药杂志2005,32(11)：1210
[56]朱代华,张兴明,郭丹.二硝基苯磺酸诱导的鼠溃疡性结肠炎动物模型[J].重庆医科大学学报,2004,29(4)：486-488
[57]王显飞,陈烨,陈村龙,等.急性结肠炎慢性化小鼠模型的建立[J].胃肠病学,2008,13(3)：167-169
[58]段征,汪维伟.溃疡性结肠炎大鼠模型研究现况[J].重庆医学,2007,第36(7)：661-662
[59]黄永年,张元德,邢玉馥.大鼠溃疡性结肠炎模型的建立与观察[J].中华病理学杂志,1995,24(6)：392
[60]白玉宾气血水相关理论和溃疡性结肠炎发病的相关性[J].辽宁中医杂志,2011,38(4)613-615
[61]刘大铭,王新月难治性溃疡性结肠炎中医病因病机探讨[J].中医杂志,2011,52(24)：2156-2157
[62]杜健鹏陈泽涛益气活血法改善微循环的实验研究[J].中国实验方剂学杂志,2006；12(9)：31-35
[63]周永学.中药寒热并用在方剂配伍中的应用[J].中华中医药杂志,2010,25(10)1543
[64]严石林,陶怡,邓瑞镇,等.从《伤寒论》探讨寒热错杂证候辨治[J].中华中医药杂志,2011,26(10)2203
[65]Chen Y, Wong RW, Seneviratne CJ, The antimicrobial efficacy of Fructus mume extract on orthodontic bracket:a monospecies-biofilm model study in vitro. Arch Oral Biol.2011 Jan;56(1): 16-21. Epub 2010 Sep 22.
[66]Kwon HA, Kwon YJ, Kwon DY, Lee JH.Evaluation of antibacterial effects of a combination of Coptidis Rhizoma, Mume Fructus. and Schizandrae Fructus against Salmonella. Int J Food Microbiol.2008 Sep 30; 127(1-2):180-3. Epub 2008 Jun 29.
[67]Round JL, Mazmanian SK. The gut microbiota shapes intestinal immune responses during health and disease Nat Rev Immunol,2009,9(5):313-323
[1]郭锦艳,陈卫.1998—2009年肠道非肿瘤性疾病住院患者临床特点调查分析[J].中国全科医学,2011.14：1334-1336
[2]Rodriguez-Perlvarez ML. Sanchez VG,et.al Role of serum cytokine profile in ulcerative colitis assessment[J].Inflamm Bowel Dis.2012 Jan 11. doi:10.1002/ibd.22865
[3]张晓博.IL-1β、IL-13、TNF-α在溃疡性结肠炎患者血清中的表达[J].河北医药2009,31(24)：3394
[4]魏思忱.IL-10在溃疡性结肠炎患者血清中的表达及意义[J].河北医药2010,32(5)559
[5]王觅柱.溃疡性结肠炎患者血清IL-lβ、TNF-α和lL-10的表达及其意义[J].国际消化病杂志,2009,29(5)：362
[6]任保从.溃疡性结肠炎患者血清IL-6、IL-8、TNF-α水平变化及意义[J].山东医药.2010,50(26)：57
[7]张晓博.溃疡性结肠炎患者血清和结肠组织白细胞介素8和白细胞介素10的表达[J].临床荟萃,2010.25(3)：210
[8]Tak PP, Firestein GS. NF-κB:a key role in inflammatory diseases[J].J Clin Invest.2001,107: 7-11.
[9]Sivaram G. Tiwari SK, Bardia A. et.al Macrophage migration inhibitory factor, Toll-like receptor 4, and CD 14 polymorphisms with altered expression levels in patients with ulcerative colitis[J].Hum Immunol.2012 Feb;73(2):201-5.
[10]李军华NF-κB、iNOS在大鼠实验性结肠炎肠组织的表达及意义[J].胃肠病学和肝病学杂志,2003,12(5)：436-439
[11|Thomas S. Baumgart DC. Targeting leukocyte migration and adhesion in Crohn's disease and ulccrative colitis[J].lnflammopharmacology.2012 Feb;20(1):1-18.
[12]范恒.理肠四方对溃疡性结肠炎大鼠血液粘附分子C044、C054的影响[J].世界华人消化杂志,2005,13(3)：398-340
[13]Sklyarov AY. Panasyuk NB, Fomenko IS. Role of nitric oxide-synthase and cyclooxygenase/lipooxygenase systems in development of experimental ulcerative colitis[J].J Physiol Pharmacol.2011 Feb:62(1):65-73.
[14]徐萍,周小江.溃疡性结肠炎组织中环氧合酶-2与一氧化氮合酶的表达及意义[J].中华消 化内镜杂志2003,20：98-399
[15]陈香宇,段芳龄,马军,等.5-氨基水杨酸对实验性结肠炎大鼠结肠粘膜NO水平的影响[J].郑州大学学报(医学版)2003,38(1)：37-39
[16]Wardle TD, Hall L, Turnberg LA. Platelet activating factor:release from colonic mucosa in patients with ulcerative colitis and its effect on colonic secretion. Gut[J].1996 Mar;38(3):355-61.
[17]Degagne E, Grbic DM, Dupuis AA, et.al P2Y2 receptor transcription is increased by NF-kappa B and stimulates cyclooxygenase-2 expression and PGE2 released by intestinal epithelial cells[J].Immunol.2009 Oct 1;183(7):4521-9. Epub 2009 Sep 4.
[18]沈琳,陈丽云,李洁.严世芸辨治溃疡性结肠炎验案1则[J].上海中医药杂志2010,44(11)：30-31
[19]黄丽,张士卿.张士卿教授治疗溃疡性结肠炎经验[J].甘肃中医学院学报,2009,26(2)：2
[20]章一凡,任光荣.任光荣治疗溃疡性结肠炎经验[J].中国现代医生,,2010,48(7)：43
[21]霍传彬.刘学勤主任医师治疗溃疡性结肠炎经验浅析[J].中医学报2009,24(5)：67-68
[22]中国中西医结合学会消化系统疾病专业委员会,2010’西昌溃疡性结肠炎中西医结合诊疗指南[J].中国中西医结合消化杂志.2011,19(1)：61-63
[23]中华中医药学会脾胃病分会.溃疡性结肠炎中医诊疗共识(2009)[J].中国中西医结合杂志,2010,30(5)：527-532
[24]郑筱萸.中药新药临床研究指导原则[M].北京：中国医药科技出版社,2002：129-134.
[25]中华中医药学会.中医内科常见病诊疗指南西医疾病部分[M].北京：中国中医药出版社,2008：107-110.
[26]国家中医药管理局.中医病证诊断疗效标准[M].南京：南京大学出版社,1994：9-10.
[27]陈爱霞,冯江雪,张磊.安肠止泻汤治疗溃疡性结肠炎42例[J].新中医2009,4l(2)：73
[28]李晟,林振文,朱子奇.白术芍药散联合传统方法治疗溃疡性结肠炎87例[J].海峡药学2009,21(8)：130
[29]刘道喜.白头翁汤加味治疗溃疡性结肠炎87例[J].江西中医药2011,10(8)：16
[30]周莺歌.半夏泻心汤治疗慢性溃疡性结肠炎58例[J].中国中医药2010,8(15)：
[31]陈小刚,曲晓璐.半夏泻心汤加味治疗慢性非特异性溃疡性结肠炎60例临床观察[J].湖南中医学院学报,2000,20(2)：49-50
[32]李志伟.补止清活汤治疗溃疡性结肠炎65例[J].中国中医急症,2010,19(3)：507
[33]胡宏中.大黄牡丹汤加减治疗溃疡性结肠炎34例[J].辽宁中医杂志第2000,27(4)：171
[34]徐彦龙,杜元灏,徐秀梅.隔药铺灸治疗慢性非特异性溃疡性结肠炎[J].中国针灸2010,30(4)：289-299
[35]任天飞.活血生肌汤灌肠治疗溃疡性结肠炎31例[J].浙江中医杂志,2000,35(7)：286
[36]鲁龙生.芍药汤治疗湿热内蕴型溃疡性结肠炎30例[J].中国中医药,2010,8(19)：11
[37]周君丰,胡敏霞.四君子汤配合痛泻要方治疗溃疡性结肠炎30例[J].陕西中医,2010,31(5)：539-540
[38]吴春江,赵双梅.痛泻要方加减治疗慢性非特异性溃疡性结肠炎50例[J].山东中医杂志,2010,29(3)：158-159
[39]樊金玲.乌梅丸合芍药甘草汤治疗慢性非特异性溃疡性结肠炎30例[J].广西中医药,19992：17
[40]谭英.乌梅丸加味治疗慢性非特异性溃疡性结肠炎48例总结[J].湖南中医杂2008,24(6)：7-8
[41]黄耀全,王志强.针灸结合四君子合剂治疗溃疡性结肠炎40例[J].广西中医药,2008,31(6)15-16
[42]梁丽.p2AR、β-arrestin2、NF-κBp65在溃疡性结肠的表达及乌梅丸的干预作用[J].世界华人消化杂志,2010,18(16)：1650-1655
[43]明彩荣,张丽红,王守岩.乌梅丸治疗大鼠溃疡性结肠炎的实脸研究[J].中国中医药科技,2007,14(1)：51
[44]殷刚峰,卜平,朱海航.白头翁加味汤调节溃疡性结肠炎大鼠血清白介素-4和肠黏膜环氧合酶-2的研究[J].中国实验方剂学杂志,2009,15(12)：84-86
[45]秦建梅,程小丽,安方玉.半夏泻心汤合四神丸加减方对溃疡性结肠炎大鼠NO、NOS及TNF-a的影响[J].甘肃中医,2010,23(6)：29-31
[46]卢健,马骥,王丽娜,等.四逆散对实验性UC大鼠血TNF-a和lL-10的影响[J].陕西中医学院学报,2010,33(6)：61-62
[47]胡旭光,利红宇.痛泻要方对肝郁脾虚型溃疡性结肠炎动物模型的治疗作用[J].广东药学院学报2004,20(1)：40-42
[48]范恒,邱明义,户菲菲,等.理肠四方对溃疡性结肠炎大鼠血液粘附分子CD44、CD54的影响[J].世界华人消化杂志,2005,13(3)：397-400
[49]吴焕淦,黄臻,刘慧荣,等.针灸对大鼠溃疡性结肠炎结肠上皮细胞凋亡影响的实验研究[J].中国针灸,2005,25(2)：119-122
[50]姚茹冰,邱明义,蔡辉,等.乌梅丸对溃疡性结肠炎大鼠病变结肠粘膜局部肿瘤坏死因子α、白介素—8及白介素—10的影响[J].中医杂志,2002,43(12)：935-936
[51]余欣邱明义,胡继鹰,等.乌梅丸对溃疡性结肠炎大鼠肠组织核转录因子-κB及细胞间黏附分子1的影响[J].中国中西医结合消化杂志,2008,16(3)：172
[52]姚茹冰,邱明义,胡兵,等.乌梅丸对溃疡性结肠炎大鼠结肠粘膜形态学的影响[J].广州中医药大学学报2003,20(1)：59-62
[53]范恒,段雪云,庄雄,等.乌梅丸对溃疡性结肠炎大鼠结肠组织NF-KBp65的影响[J].世界华人消化杂志2008,16(8)：896-899
[54]范恒,邱明义,梅家俊,等.乌梅丸对溃疡性结肠炎大鼠组织细胞因子的干预效应[J].中国临床康复,2006,10(7)：87-89
[55]姚民武,李保良,黄水清.乌梅丸对溃疡性结肠炎患者血清TNF—a、IL—6及IL—8含量的影响[J].医学信息,2010,8：2188-2189
[56]陈林,陈鸿平,刘友平.乌梅不同部位药理作用研究[J].中国药房,2007,18(27)：2089-2090
[57]刘友平,陈鸿平,万德光.乌梅的研究进展[J].中药材,2004,27(6)：459-461
[58]李仲兴,王秀华,张立志,等.应用M--H琼脂进行五倍子等5种中药对28株肠球菌的体外抗菌活性观察[J].中草药,2001,32(12)：1101
[59]张明发,沈雅琴,朱自平,等.干姜温中止痛作用的研究[J].两北药学杂志,1996,11(4)：186
[60]王梦,钱红美,苏简单.干姜乙醇提取物解热镇痛及体外抑菌作用研究[J].中药新药与临床药理,2003,14(5)：299.
[61]中药药理学沈映君人民卫生出版社北京2000：494-495
[62]陈玉春.人参附子与人参附子汤免疫调节作用机理初探[J].中成药1994,16(8)：30
[63]肖庆慈.肉桂赤石脂的配伍研究[J].云南中医学院学报1996,19(4)：1
[64]陈家源牙启康卢文.中药肉桂的研究概况[J].广西医学2009,31(6)：872-874
[65]朱自平.张明发.沈雅琴,等.肉桂的温中止痛药理研究[J].中国中药杂志.1993,18(9)：553-557.
[66]张明发.花椒抗脾胃虚寒证的药理作用研究[J].中药药理与临床,1994,10(2)：37
[67]欧阳杰湖,潘善庆,陈子渊.刺壳花椒提取物消炎镇痛作用的实验研究[J].中医药导报,2008,14(12)：71-73
[68]王秀杰黄连的药理研究及现代应用[J].中国药师,2003,6(6)：370
[69]李波,朱维良,陈凯先.小檗碱及其衍生物的研究进展[J].药学学报,2008,43(8)：773-787
[70]杨周平,武志军.中药黄柏的药理作用和临床应用研究[J].甘肃医药,2010,29(3)329-330
[71]张琛,赵钢.人参皂苷Rd的药理作用研究进展[J].中国新药杂志,2011,20(11)：953-957
[72]李宗友 节译.人参根中果胶多糖的细胞保护作用[J].国外医学-中医中药分册,1992,14(2)：21
[73]胡竟一,邱春燕,雷玲细辛的镇痛和抗炎作用[J].中药药理与临床,2011,27(2)：68-69
[74]程小平,吴国泰,刘峰林.当归挥发油对实验性胃肠动力障碍的作用及机制研究[J].中药药理与临床2011；27(4)54-56
[75]王瑞琼,吴国泰,任远,等.当归挥发油对兔离体胃肠平滑肌张力的影响[J].甘肃中医学院学报,2010：27(2)：12-14
[76]乐江,彭仁,孔锐,等.当归粗多糖镇痛作用的实验研究[J].中国药学杂志,2002,37(10)：746-748.
[77]许济群.方剂学[M]上海：上海科技出版社,1993
[78]李伟东,蔡宝昌.中药复方研究思路的探讨[J].中药新药与临床药理,2004,15(3)216-218
[79]韩凌,王钦茂.方剂拆方的研究进展[J].中国实验方剂学杂志,2000,6(1)：63
[80]荆鲁,王阶,花照泉,等.中药复方配伍及拆方研究概况[J].中国中药杂志,2003,28(12)：1125-1128
[8]]邓子华,邓虹珠.中药复方拆方研究概况[J].现代中西医结合杂志,2007,16(4)：563-564
[82]高晓山.中药药性论[M].北京：人民卫生出版社,1992：256
[83]王钦茂,周光友.中药复方拆方研究概况[J].安徽中医学院学报,996,15(2)：59-61.
[84]贺又舜.方剂研究的一些思考[J].湖南中医药导报,2003,9(2)：42-44.