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Effect Of Xiezhuojiedu Decoction On TLR4, IL-13, MD2 On Ulcerative Colitis Model Rats

Posted on:2016-09-03Degree:MasterType:Thesis
Country:ChinaCandidate:Q Y YangFull Text:PDF
GTID:2284330461462026Subject:Chinese medical science
Abstract/Summary:PDF Full Text Request
Objective: Ulcerative colitis is a kind of chronic nonspecific inflammatory disease which has a long disease course, complex etiology and different disease severities, easy to repeated attacks, difficult to be cured, and has a certain relationship with the incidence of colon cancer. In recent years, the morbidity of UC increased constantly, which has drew wide attention. During a large number of Clinical Practice in a long time, we selected an experienced Pre scription named Xiezhuojiedu Decoction based on Turbidity Toxin theory to treat this disease, with the method of purging turbidity and ascending lucidity, detoxification and removing stasis, it has reliable effects. This is an experimental study on the base of past work, through the animal experiment,to observe the influence of this method on ulcerative colitis serum IL-13, TLR4 and MD2, explore the mechanism and material base of UC, and explain the mechanism of Xiezhuojiedu Decoction on UC, so as to lay a foundation for further clinical study.Method: In this study, 45 healthy and clean wistar Rats were taken, male, weighing 220~250g. 8 of them were randomly selected as the blank group(BK), the other rats copy the animal models of ulcerative colitis with Trinitrobenzene sulfonic acid(2,4,6-trinitrobenzene-sulfonic acid, TNBS) /ethanol joint modeling method. Three days later, five model rats were randomly selected to be killed, to check for the colon specimens and confirm that there was congestion, edema, ulcer formation and pathological changes. After the modeling,randomly divided the remaining rats into four groups, named modeling group(MK), Xiezhuojiedu Decoction high dose group(GK), Xiezhuojiedu Decoction low dose group(DK), SASP group(LK), with 8 rats in each group. BK rats were fed normally, MK rats were given normal saline by intragastric administration, LK rats were given SASP by intragastric administration, GK rats were given Xiezhuojiedu Decoction high dose by intragastric administration,and DK rats were given Xiezhuojiedu Decoction low dose by intragastric administration, the treatment lasting for 14 days. The experiment was studied and discussed from three aspects: to observe the changes of body weight, mental status, general changes in stool, etc; to evaluate the colonic mucosa damage degree; to observe the expression on ulcerative colitis serum IL-13, TLR4 and MD2. The main object of this study is to observe the effect of Xiezhuojiedu Decoction on the influence of ulcerative colitis serum IL-13, TLR4 and MD2, and analyse the possible mechanism of this Decoction on Ulcerative Colitis.Results:1 The rats’ general condition:Compared with BK, the general condition of other rats in all the g r o u p s c h a n g e d d i f f e r e n t l y. A f t e r t h e d r u g i n t e r v e n t i o n, t h e rats in GK has granular stool,reacted rapidly, liked to move, ate more, and the weight grew quickly, the hair became bright and soft, the general condition was better than other treatment groups, close to control group. The condition of LK group and DK group were similar, by contrast, MK group was the worst.2 Disease active index(DAI):Compared with BK group, DAI score of rats in MK, DK, LK, GK groups increased, the differences had statistical significance(P<0.05). DAI score of BK rats(0.382±0.081) didn’t rise obviously, the score of MK rats(2.531±0.313) increased quickly, the difference between two groups had statistical significance(P<0.05). Compared with MK, DAI score of GK(0.495±0.128), DK(1.687±0.144), LK(1.692±0.225) rats decreased significantly, had significant difference(P<0.05). Compared with LK, DAI score of GK rats was lower, had significant difference(P<0.05); but with DAI score of DK rats didn’t have significant difference(P>0.05). Compared between GK and DK, DAI score of GK rats was obviously lower than DK, had significant difference(P<0.05).3 The general observation on the rats’ colon and colonic mucosa damage index(CMDI) :By the visual observation, the rat’s colon mucosa was smooth, there were no congestion, edema, ulcer, colonic wall thickening, etc in BK group. Colon mucosa of MK group could be observed congestion, edema, erosion, ulcer, bleeding, colonic wall thickening and expansion. After medicinal treatment, the situation of GK, DK, LK groups were better than MK group. Compared with BK, the CMDI scores of MK, DK, LK, GK groups were higher, the difference was statistically significant(P<0.05). Compared with MK, the CMDI scores of DK, LK, GK rats were lower, the difference was statistically significant(P<0.05). Compared with LK, CMDI score of GK rats was lower, had significant difference(P<0.05); but with CMDI score of DK rats didn’t have significant difference(P>0.05). Compared between GK and DK, CMDI score of GK rats was obviously lower than DK, had significant difference(P<0.05).4 The observation under the light microscope:The colon tissue under the light microscope of BK group rats had clear structure, without congestion, edema, erosion and ulcer, mucosal epithelial cells arranged in neat, colon glands were structure. Compared with BK rats, other groups of rats had changes differently in inflammatory cells infiltration degree of colon musosal, epithelial integrity degree, gland structure, etc. MG rats had deletion in colon mucosa layer, there were a large number of inflammatory cell in submusoca, different degrees of congestion we could be found, edema, erosion and ulcer, in the bottom of the ulcer lesions, acute vasculitis could be seen. After drug intervention, colon mucosa pathological of each treatment group rats eased in different degrees, which DK and LK rats, colon ulcer shallowed, degree of erosion and desquamation in colon mucosa eased, the ulcer epithelium repaired obviously, a small amount of inflammatory cell infiltrationed crypt intestinal glands and interstitial. GK rats had no significant congestion and edema, intestinal glands arranged in neat rows, interstitial scattered a small amount of inflammatory cells, goblet-cell abundant, the degree of recovery was close to the BG.5 The test results of serum IL-13, TLR4, MD2:Compared with the BK rats(58.9638±2.6158), the IL-13 level in serum of the MK rats(37.3388±1.0003) decreased obviously, had significant difference, the difference was statistically significant(P<0.05); Compared with the MK rats, the IL-13 level in serum of the GK rats(53.1175±2.0330), DK rats(43.2775±3.6927), LK rats(43.9850±3.3698) increased obviously, had significant difference, the difference was statistically significant(P<0.05); Compared with the LK and the DK rats, the IL-13 level in serum of the GK rats increased obviously, had significant difference, the difference was statistically significant(P<0.05); Comparing between the DK rats and LK rats, the difference was not statistically significant(P>0.05); Compared with the BK rats(0.1588±0.0030), the TLR4 level in serum of the MK rats(0.4427 ±0.1633) increased obviously, had significant difference, the difference was statistically significant(P<0.05); Compared with the MK rats, the TLR4 level in serum of the GK rats(0.2008±0.0028), DK rats(0.2367±0.0063), LK rats(0.2608±0.1469) decreased obviously, had significant difference, the difference was statistically significant(P<0.05); Compared with the LK and the DK rats, the TLR4 level in serum of the GK rats decreased obviously, had significant difference, the difference was statistically significant(P<0.05); Comparing between the DK rats and LK rats, the difference was not statistically significant(P>0.05); Compared with the BK rats(0.1075±0.0018), the MD2 level in serum of the MK rats(0.3072±0.0060) increased obviously, had significant difference, the difference was statistically significant(P<0.05); Compared with the MK rats, the MD2 level in serum of the GK rats(0.1263±0.0023), DK rats(0.2009±0.0062), LK rats(0.2003±0.0056) decreased obviously, had significant difference, the difference was statistically significant(P<0.05); Compared with the LK and the DK rats, the MD2 level in serum of the GK rats decreased obviously, had significant difference, the difference was statistically significant(P<0.05); Comparing between the DK rats and LK rats, the difference was not statistically significant(P>0.05).Conclusion: Xiezhuojiedu Decoction can improve the general condition and colonic organization form of the Ulcerative Colitis Rats obviously, with the decrease of colonic mucosa damage index and the pathological damage score of Ulcerative Colitis Rats; Xiezhuojiedu Decoction can decrease the level of TLR4 and MD2 in the serum on Ulcerative Colitis Rats, and improve the level of IL-13 in the serum on Ulcerative Colitis Rats; The results proved the effect of Chinese medicine Xiezhuojiedu Decoction on Ulcerative Colitis Model Rats, the therapeutic mechanism is possibaly related to the enhancement of the level of IL-13 and the inhibition of TLR4 and MD2 expression level.
Keywords/Search Tags:Ulcerative colitis, Animal experiment, Xiezhuojiedu Decoction, TLR4, IL-13, MD2
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