| 1.ObjectiveTo investigate therapeutic effect and mechanism of Modified qingchangjiedu Decoction by exploring its effect on inflammatory cytokine related indicators and platelet activation in TNBS/ethanol induced rat ulcerative colitis model.2.Method60 SPF SD rats were randomized into blank group, model group, western medicine group, traditional Chinese medicine (TCM) high-dose group, TCM mediate dose group and TCM low-dose group with 10 rats in each group. TNBS/ethanol induced ulcerative colitis model was used in all of the groups, except the blank group. Medicine was given 4 weeks after modelling for consecutive 2 weeks. In blank and model groups, equal volume of saline was given by gavage; in west medicine group, mesalazine sustained release granules were given; Modified qingchangjiedu Decoction was given by gavage in TCM groups. TNF-a, PC, TXB2,6-Keto-PGFia in plasm of the rats were tested at different time points on Day 7 and Day 14; all of the rats were executed on day 14, and colon tissue pathology was scoring, immunohistochemical test of IL-1β, IL-6, IL-8 and IL-10 was made in colon tissue, and genetic expression of TLR4 and NF-κB in colon tissue was also tested by PCR.3.Results(1) In TNBS/ethanol induced rat ulcerative colitis model, the rats experienced diarrhea, blood stool, decreased body weight and poor spirit after modelling, which were relieved gradually after treatment;(2) Compared with blank group, colon tissue injury in model group was consistent with typical UC features with significantly increased pathological score (P<0.01); compared with model group, pathological scores in various treatment groups were significantly decreased (P<0.01, P<0.05);(3) Compared with blank group, IL-1β content in colon tissue in model group was significantly increased (.P<0.01); compared with model group, IL-1β content in colon tissue was decreased in treatment groups (P<0.05,P<0.01);(4) Compared with blank group, IL-6 content in colon tissue in model group was significantly increased (P<0.01); compared with model group, IL-6 content in colon tissue was decreased in treatment groups (P<0.05);(5) Compared with blank group, IL-8 content in colon tissue in model group was significantly increased (P<0.01); compared with model group, IL-8 content in colon tissue was decreased in treatment groups (P<0.01,P<0.05);(6) Between blank groups, no statistical difference was found on different time points (P> 0.05); compared with blank group, TNF-α content in colon tissue in model group was significantly increased (P<0.01);compared with model group, TNF-a content in colon tissue was decreased in all other treatment groups except TCM low-dose group (P<0.05,P<0.01);(7) Compared with the blank group, IL-10 content in colon tissue in model group was significantly decreased (P<0.01), which was consistent with UC model features; compared with model group, IL-10 expression in colon tissue was increased in treatment groups (P<0.05, P<0.01);(8) Compared with the blank group, expression of TLR4 and NF-κB in colon tissue in model group was significantly increased (P<0.01);compared with model group, the expression was decreased after treatment with Modified qingchangjiedu Decoction (P<0.01), while no statistical difference was found between TCM groups and Western medicine group;(9) Compared with blank group, PC in colon tissue in model group was significantly increased (P<0.01); compared with model group, platelet count in colon tissue was decreased in treatment groups, and the differences in Western medicine and TCM high-dose group have statistical significance (P<0.05);(10) Between blank groups, no statistical difference was found on different time points (P> 0.05); compared with blank group, plasm TXB2 in model group was significantly increased on different time points (P< 0.01); compared with model group, plasm TXB2 were decreased at different time points in all treatment groups except low-dose group (P<0.05, P<0.01)(11) Between blank groups, no statistical difference was found on different time points (P>0.05); compared with blank group, plasm 6-Keto-PGF1α in model group was increased on different time points (P<0.05); compared with model group;plasm 6-Keto-PGF1α were increased at different time points in all treatment groups (P< 0.05, P<0.01)(12) Between blank groups, no statistical difference was found on different time points (P>0.05); compared with blank group, TXB2/6-Keto-PGF1α ratio in model group was increased on different time points(P<0.01); TXB2/6-Keto-PGF1α ratio were decreased on different time points in all treatment groups (P<0.05, P<0.01)4. Conclusion(1) Modified Qingchangjiedu Decoction can improve the histopathologic score, clinical manifestation, and recover of body weight of rats;(2) Modified Qingchangjiedu Decoction can inhibit the expression of pro-inflammatory cytokines IL-1(3, IL-6, IL-8 and TNF-a, enhance the expression of 1L-10 and regulate inflammatory cytokine nets, which may be the mechanism of its action for TNBS/ethanol induced rat ulcerative colitis;(3) Modified Qingchangjiedu Decoction can inhibit the expression of TLR4and NF-kB, and then inhibit the release of downstream inflammatory cytokines, which may be related to the mechanism of its action for rat ulcerative colitis;(4) Modified Qingchangjiedu Decoction can down regulate plasm TXB2 level, upregulate 6-Keto-PGF1α, decrease TXB2/6-Keto-PGF1α ratio, decrease PC and improve hypercoagulable state of blood, which may be related to the mechanism of its action for rat ulcerative colitis;... |
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