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Effect Of Xiezhuojiedu Decoction On TLR2,IL-1β,IL-4on Ulcerative Colitis Model Rats

Posted on:2011-05-16Degree:MasterType:Thesis
Country:ChinaCandidate:X M LangFull Text:PDF
GTID:2154360308474326Subject:Chinese medical science
Abstract/Summary:PDF Full Text Request
Objective:Ulcerative colitis is a kind of chronic nonspecific inflammation which has a long disease course, different disease severities and has a certain relationship with colon cancer attack,it has been recommended to be one of the refractory diseases by World Health Organization. During the long Clinical Practice we selected an experienced prescription named Xiezhuojiedu Decoction based on Turbidity Toxin theory of traditional chinese medicine 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 to observe and study the mechanism and material base of UC,and also the mechanism of Xiezhuojiedu Decoction on UC,so as to lay a foundation for further clinical study.Methods:In this study,40 healthy and clean wistar Rats were taken,half male and half female,weighing 250g and were randomly divided into 5groups with 8 rats in each group.They are separately named control group (BK),modeling group(MK),Xiezhuojiedu Decoction high dose group (GK),Xiezhuojiedu Decoction low dose group(DK),SASP group(LK).2,4,6-trinitro benzene-sulfonic acid,TNBS/ethanol combinative method of establishing model was used to Induce animal models in Rat Ulcerative Colitis.3 days after model making,BK rats were fed normally,MK rats were given normal saline by gavage,MK rats were given SASP by gavage, GK,DK rats were separately given Xiezhuojiedu Decoction high dose and Xiezhuojiedu Decoction low dose by gavage for 14 day.I studied and discussed the experiment from three aspects:Experiment 1, to observe the effect of Xiezhuojiedu Decoction on general condition and pathological effect on Ulcerative Colitis Model Rats;Experiment 2, to observe the effect of Xiezhuojiedu Decoction on TLR2mRNA and TLR2 protein expression of the colonic mucosa on Ulcerative Colitis Model Rats;Experiment 3,to observe the effect of Xiezhuojiedu Decoction on IL-1β,IL-4 on Ulcerative Colitis Model Rats.The main object of this study is to observe the effect of this decoction and elucidate the possible mechanism of Xiezhuojiedu Decoction on Ulcerative Colitis.Results:1 Experiment 1 Effect of Xiezhuojiedu Decoction on general condition and pathological effect on Ulcerative Colitis Model Rats1.1 The rats'general condition and disease active index (DAI)Compared with BK,all those mental status,activity condition,hair glossiness,appetite,defecate character of the rats in all the treatment groups changed differently.After the drug intervention,the rats in GK liked to move, responded rapidly,the weight grew quickly,ate more,stool was granular,a week later the hair became bright and soft,the general condition was better than other treatment groups,close to control group.DAI of BK rats didn't rise obviously,DAI of MK rats grew quickly,the differences between two groups had statistical significance(P<0.01),Compared with BK, DAI of GK(0.437±0.125),DK(1.332±0.141),LK(1.285±0.234)rats decreased significantly,had significant difference (P<0.01).Compared with LK, DAI of GK rats decreased significantly, had significant difference (P<0.01); DAI of DK didn't have significant difference(P>0.05).Compared between GK, DK, DAI of GK rats was definitely lower than DK,had significant difference (P<0.01).1.2 The general observation on the rats'colon and colonic mucosa damage index (CMDI)Compared with BK,there were changes in the colon colour,integrity degree of plica,thickness and hyperemia,edema in all the treatment groups. After the drug intervention,The colon of GK rats dilated little,tube wall was thick,the colour othe tube wall didn't change significantly,tere was not erosion and ulsers,but there were scars of the ulsers,the condition was better than the other treatment groups.CMDI of BK rats (0.463±0.122) didn't rise obviously,CMDI of MK rats (2.620±0.458) grew quickly,the differences between two groups had statistic-cal significance(P<0.01).Compared with MK,CMDI of GK (0.478±0.133), DK (1.554±0.101),LK(1.514±0.173)rats decreased significantly,had signifi-cant difference (P<0.01).Compared with LK,CMDI of GK rats decreased sign-ificantly,had significant difference (P<0.01);CMDI of DK didn't have signifi-cant difference(P>0.05).Compared between GK,DK,CMDI of GK rats was definitely lower than DK, had significant difference(P<0.01).1.3 The pathological histomorphology observation of rats'colon under the light microscope and the lesion classificationThree days after model making, there were edema,necrosis,ulcers,infla mmatory exudation,mucous layer lost,ect. After the drug intervention,rats' colon in GK was just like BK,congestion and edema were not obvious,inflammatory cells were interspersed,mucosa epithelium and crypt were tidy,goblet cells were rich.The lesion classification of BK (1.625±0.744) under the light microscope didn't rise obviously, the lesion classification of MK rats (4.250±0.707) grew quickly,and the differences between two groups had statistical significance (P<0.01).Compared with MK,the lesion classification of GK(3.250±0.707),DK (2.3750.744),LK(3.1250.641)rats decreased significantly,had significant difference (P<0.01).Compared with LK, the lesion classification of GK rats decreased significantly,had significant difference (P<0.01);the lesion classify-cation of DK didn't have significant difference(P>0.05).Compared between GK and DK, the lesion classification of GK rats was definitely lower than DK, had significant difference(P<0.01).2 Experiment 2 to observe the effect of Xiezhuojiedu Decoction on TLR2mRNA and TLR2 protein expression of the colonic mucosa on Ulcerative Colitis Model Rats2.1 The effect of Xiezhuojiedu Decoction on TLR2mRNA expression of the colonic mucosa on Ulcerative Colitis Model Rats TLR2mRNA expression of the colonic mucosa onBK (0.070±0.002) rats was little, TLR2mRNA expression of the colonic mucosa on MK (0.414±0.006) rats increased significantly, the differences between two groups had statistical significance(P<0.01).Compared with MK, TLR2mRNA expression of the colonic mucosa on GK(0.253±0.019),DK(0.326±0.038),LK (0.282±0.228) rats decreased obviously, had significant difference (P<0.01). Compared with LK, TLR2mRNA expression of the colonic mucosa on GK rats decreased significantly, had significant difference (P<0.01). TLR2mRNA expression of the colonic mucosa on DK rats decreased, had significant difference (P<0.05). Compared between GK,DK, TLR2mRNA expression of the colonic mucosa onGK rats decreased significantly, had significant difference (P<0.01).2.2 The effect of Xiezhuojiedu Decoction on TLR2 protein expression of the colonic mucosa on Ulcerative Colitis Model RatsTLR2 protein expression of the colonic mucosa on BK (8.811±1.808) rats was little, TLR2 protein expression of the colonic mucosa on MK (51.535±2.911) rats increased significantly,the differences between two groups had statistical significance(P<0.01).Compared with MK,TLR2 protein expression of the colonic mucosa on GK (16.728±1.439),DK (34.013±2.414),LK (34.941±2.308) rats decreased obviously, had significant difference (P<0.01). Compared with LK,TLR2 protein expression of the colonic mucosa on DK rats didn't have significant difference (P>0.05); TLR2 protein expression of the colonic mucosa on GK rats decreased, had significant difference (P<0.01). Compared between GK and DK, TLR2 protein expression of the colonic mucosa on GK rats decreased significantly,had significant difference (P<0.01).3 Experiment 3 to observe the effect of Xiezhuojiedu Decoction on IL-1β, IL-4 on Ulcerative Colitis Model Rats.3.1 The effect of Xiezhuojiedu Decoction on IL-1βon Ulcerative Colitis Model Rats.IL-1βof the serum on BK (0.086±0.030) rats was little,IL-1βof the serum on MK (0.209±0.050) rats increased significantly,the differences between two groups had statistical significance (P<0.01).Compared with MK, IL-1βof the serum on GK (0.082±0.013),DK (0.137±0.029),LK (0.128±0.041) rats decreased obviously,had significant difference (P<0.01).Compared with LK, IL-1βof the serum on DK rats didn't have significant difference (P>0.05); IL-1βof the serum on GK rats decreased,had significant difference (P<0.05). C-ompared between GK and DK, IL-1βof the serum on GK rats decreased sign-ificantly, had significant difference (P<0.01).3.2 The effect of Xiezhuojiedu Decoction on IL-4on Ulcerative Colitis Model Rats.IL-4 of the serum on BK (1.163±0.263) rats was rich,IL-4 of the serum on MK (0.443±0.142) rats decreased significantly,the differences between two groups had statistical significance(P<0.01).Compared with MK,IL-4 of the serum on GK (1.024±0.177),LK (0.892±0.153) rats increased obvi ously,had significant difference (P<0.01); IL-4of the serum on DK (0.688±0.212) increased,too,had significant difference (P<0.05).Compared with GK, IL-4of the serum on LK rats didn't have significant difference (P>0.05); Com-pared with DK, IL-4 of the serum on LK rats had significant difference (P<0.05).Compared between GK and DK, IL-4of the serum on GK rat increased significantly,had significant difference (P<0.01).Conclusion:Xiezhuojiedu Decoction can improve the rats'general condition and colonic organization form;Xiezhuojiedu Decoction can decrease TLR2m RNA and TLR2 protein expression of the colonic mucosa on Ulcerative Col itis Model Rats;Xiezhuojiedu Decoction can decreaseIL-1βcontent,improve IL-4 level,The results proved the effect of Chinese medicine Xiezhuojiedu De-coction on Ulcerative Colitis Model Rats,the therapeutic mechanism is possi-baly related to its influence on TLR2mRNA and TLR2 protein expression,IL-1βcontent,IL-4 level.
Keywords/Search Tags:ulcerative colitis, animal experiment, Xiezhuojiedu Decoction, TLR2mRNA, TLR2 protein expression, IL-1β, IL-4
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