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Study On The Efiect Of Wumei Pill And Its Subdivisions On Cell Factors,Inflammatory Mediators And TLR4/NF-κB Signal Pathway Of Ulcerative Colitis In Rats

Posted on:2013-11-19Degree:DoctorType:Dissertation
Country:ChinaCandidate:S G YanFull Text:PDF
GTID:1224330395956049Subject:Traditional Medical Formulae
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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.
Keywords/Search Tags:Ulcerative colitis, Wumei Pill, Subdivisions, Cold and heatapplication, Cytokines, Inflammatory mediators
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