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The study on the mechanism of Gancao Xiexin Decoction on TNBS colitis ratsObjective:To observe the curative effect of Gancaoxiexin Decoction on ulcerative colitis model rats.It also focuses on how Gancaoxiexin regulates related molecules in the pathways of ulcerative colitis rats model of interleukin-6/Signal transducer and activator of transcription 3(Interleukin-6/Signal transducer and activator of transcription 3,IL-6/STAT3)and its ultimate influence on Claudin-1.The purpose is to study the mechanism,safety and the relationship between dose and effect when treating ulcerative colitis with Gancaoxiexin Decoction.Methods:60 SD rats were randomly divided into 6 groups,namely blank group,model group,mesalazine group(5-ASA group),Gancaoxiexin Decoction low dose group(GCXX-L group),Gancao Xiexin Decoction medium dose group(GCXX-M group)and Gancaoxiexin Decoction high dose group(GCXX-H group).There were 10 rats in each group.Every group,except the blank group,was made a model with TNBS.Then the blank group and model group were given a gavage with normal saline,while the 5-ASA group,GCXX-L group,GCXX-M group and GCXX-H group were given mesalazine,Gancaoxiexin Decoction of a low dose,Gancaoxiexin Decoction of a medium dose and Gancaoxiexin Decoction of a high dose respectively.The treatment lasted for 14 days,during which the general conditions of rats were observed,and their defecation and weight change were recorded too.After 14 days,blood serum was extracted to detect the amount of ALT,AST,BUN and Cr,and the level of IL-6 in peripheral blood was also checked by means of ELISA.The rats were later killed.A general observation on liver,kidney and colon was carried out and pathological observation were done with microscopes.Immunohistochemistry was used to analyze the expression of IL-6,Claudin-1,STAT3 and phosphate STAT3(P-STAT3)in the colonic tissue.The frozen stored colon tissue was detected through Real-time PCR method to find out the expression of PCR IL-6 mRNA,Claudin-1 mRNA,STAT3 mRNA in each group.Results:Compared with the blank group,rats of model group showed a phenomenon of perianal fur with fecal contamination and decrease in weight(P<0.01).Their serum AST content increased obviously(P<0.01).However,ALT,BUN and Cr had no change(P>0.05).The expression of IL-6 in peripheral blood of rats of model group significantly rose(P<0.01)and their score in pathology and colon were significantly increased(P<0.01).In addition,the expression of IL-6,STAT3 and P-STAT3 in colonic tissue went up(P<0.01),while Claudin-1 dropped obviously(P<0.01).The expression of IL-6 mRNA and STAT3 mRNA rose(P<0.01)and that of Claudin-1 mRNA dropped(P<0.01).Compared with the model group,with the treatment of mesalazine or Gancao Xiexin Decoction,the time of fecal contamination on perianal fur of the rats was shortened(P<0.01),and the rats' weight increased(P<0.01).Except the 5-ASA group,the content of serum AST decreased(P<0.01).The expression of IL-6 in peripheral blood decreased significantly(P<0.05).Except the GCXX-L group,colon gross score and pathological score decreased(P<0.05).The expression of IL-6,STAT3 and P-STAT3 in colon tissue decreased(P<0.05)while the expression of Claudin-1 increased(P<0.05).The expression of IL-6 mRNA and STAT3 mRNA decreased(P<0.01)while the expression of Claudin-1 mRNA increased(P<0.01).Conclusion:Gancao Xiexin Decoction can improve the general symptoms of TNBS ulcerative colitis rats,reduce the pathogenesis and histological changes of the colon,and achieve satisfactory results even with a medium dose.The mechanism may be related to its abilities to decrease expression of tissue and peripheral blood IL-6,inhibit IL-6/STAT3 signaling pathway,reduce the expression and activation of STAT3,increase the expression of Claudin-1 in colon and recover colonic mucosal mechanical barrier.The experimental observation showed no obvious toxicity to the liver of TNBS ulcerative colitis rats.Part ? Clinical observation on the effect of Gancao XiexinDecoction Combined with mesalazine on ulcerative colitisObjective:To assess the efficacy and safety of Gancao Xiexin Decoction through a systemic observation in the treatment of ulcerative colitis(Cold-Heat Complication).Methods:By means of random positive drug control,37 adult patients with ulcerative colitis who belong to Cold-Heat Complication were divided randomly into 19 cases in the treatment group and 18 cases in the control group.The treatment group was treated with Gancao Xiexin Decoction,with one dose per day for twice,and at the same time they took mesalazine sustained-release particles orally at the dose of each time 1g for 4 times per day.The control group was treated orally with mesalazine sustained-release particles at the dose of each time 1g for 4 times per day.Two groups were both treated for 4 weeks.The curative effect of the two groups was compared in the form of TCM symptom score and modified Mayo score.The blood routine,liver and kidney function were compared between the two groups before and after the treatment.Results:2 cases in treatment group and 1 case in congrol group were lost.The total effective rate of treatment group was 76.5%,and the total effective rate of control group was 76.5%,with no significant difference between the two groups(P>0.05).The total effective rate of treatment group of TCM syndrome was 88.3%,while that of the control group was 70.6%,with no significant difference between the two groups(P>0.05).After treatment,the modified Mayo scores of the two groups were significantly decreased(P<0.01),without any significant difference between them(P>0.05).The TCM syndrome score of the two groups were significantly decreased(P<0.01)after treatment,and the treatment group was significantly lower than the control group(P<0.05).Before and after treatment,there was no significant difference in WBC,RBC,Hb,Pit,ALT,AST,BUN and Cr between the two groups(P>0.05).Conclusion:The main TCM syndrome of Ulcerative colitis can be obviously released by Gancao Xiexin Decoction combined with mesalazine.No side effect of hematological system,liver and kidney was found. |
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