| Objective:To investigate the effect of Qixian Yijiang decoction on clinical efficacy,inflammatory response and oxidative stress in patients with Ulcerative Colitis.To observe the effect of the main component,astragaloside ?,on the intestinal mucosal barrier and TLRs/NF-?B pathway in DSS-induced UC model rats.Sequentially,reveal the pathological mechanism of UC on the molecular level,explore the mechanism of Qixian Yijiang decoction and its component astragaloside ? in the treatment of UC.Methods:100 patients with UC were selected,the patients were randomly divided into QXYJ group and mesalazine group with 50 cases in each group,according to the digital table method,performe control observation with double-blind,randomized,positive drug.The QXYJ group received with QXYJ decoction,while the mesalazine group received with mesalazine SR granules.Observe clinical efficacy,TCM symptoms,colonic mucosa and pathological changes in two groups.Detect several laboratory indicators,including CRP?ESR,IL-6?IL-8?IL-10?TNF-??SOD?MDA before and after treatment in the two groups.In the experimental study,the 60 DSS-induced UC rats were randomly divided into 6 groups,including the blank group,the model group,the low,medium and high astragaloside group and the mesalazine group.Drug intervention was given separately to observe changes in rats before and after intervention:General conditions,length of colon,macroscopic observation of colonic mucosa and pathology;The level of IL-1?,TNF-?,IL-4,SOD,MDA;The protein expression level of ICAM-1,MMP9 and TLR2,TLR4,NF-kB p65.Results:The clinical study of Qixian Yijiang decoction intervention in UC patients showed that after treatment,the clinical effective rate in the QXYJ group is 90%,while the rate in the mesalazine group is 76%,the difference was statistically significant(P<0.05).After treatment,the symptom score of diarrhea,abdominal pain,mucus pus and blo.od,and the total symptom score in the QXYJ group were significantly better than the scores in the mesalazine group,the difference was statistically significant(P<0.05).After treatment,the efficacy of TCM syndrome scores in the QXYJ group was significantly better than the scores in the mesalazine group,the difference was statistically significant(P<0.05).Compared the tongue and pulse in the two groups before and after treatment,the QXYJ group had significant improvement on the tongue mark,and the mesalazine group showed no significant improvement,the difference was statistically significant(P<0.05).The improvement of red tongue,dark red tongue and ecchymosis in the QXYJ group was better than that in mesalazine group,the difference was not statistically significant(P>0.05).Meanwhile,the white greasy tongue and yellow greasy tongue in the two groups were significantly improved,the QXYJ group was superior to the mesalazine group,and the difference was statistically significant(P<0.05).The QXYJ group was significantly better than the mesalazine group in the reduction of string slip,virtual slip,slippery and slippery pulse(P<0.05).After treatment,the Baron score in the QXYJ group was significantly lower than that in the mesalazine group(P<0.01),the degree of improvement of congestion,edema and ulcer was significantly better than that of mesalazine group(P<0.05),and the improvement of erosion was similar in both groups(P>0.05).After treatment,the modified Mayo total score in the QXYJ group was significantly lower than that of the mesalazine group(P<0.05).After treatment,the QXYJ group improved the levels of SOD,MDA,ESR,CRP and the inflammatory factors IL-6,IL-8,IL-10.The improvement of TNF-? level was significantly better than that of mesalazine group(P<0.01).And there was no adverse events occurred.Experimental study on the effects of astragaloside on DSS-induced UC model rats showed that:1.colon length:After intervention,compared with the model group,the length of colon was shortened in the three groups of AS-?and the mesalazine group.The improvement of colon length in the high AS-?group was similar to the mesalazine group(P>0.05);2.DAI,CDMI and histopathological scores:After intervention,compared with the model group,the DAI,CDMI and histopathological scores of each AS-?groups and the mesalazine group were significantly lower(P<0.05),the improvement of DAI and CDMI score in the high AS-? group and mesalazine group were similar to each other(P>0.05);3.inflammatory factors,oxidative stress factors:After intervention,compared with the model group,the levels of IL-1?,TNF-?,IL-4,SOD and MDA in UC rats were significantly improved in each AS-? groups and the mesalazine group(P<0.05),the high AS-?group was significantly better than the mesalazine group(P<0.05).The improvement of the level of IL-1?,TNF-? and SOD activity in the high AS-? group was similar to that of mesalazine(P>0.05).However,the improvement of MDA level was not as good as mesalazine(P<0.05);4.Adhesion molecules and matrix metalloproteinases:After intervention,compared with the model group,the expressions of ICAM-1 and MMP9 in colon tissue of each AS-? groups and the mesalazine group were significantly lower than those in the model group,and the difference was statistically significant(P<0.01).The relative expression of ICAM-1 in the high-dose AS-? group was lower than that in the mesalazine group(P<0.05).While,the relative expression of MMP9 protein in the two groups was similar,and the difference was not statistically significant(P>0.05);5.TLRs/NF-?B signaling pathway:After intervention,compared with the model group,the expressions of TLR2,TLR4,IKKa and NF-?B p65 in colon tissue of each AS-? groups and the mesalazine group were decreased on different degrees(P<0.01).The expression of TLR2,TLR4 and NF-?B p65 in the middle and high AS-? group were similar to those in the mesalazine group(P>0.05).While,the expression of IKKa in the middle and high AS-? group was statistically lower than that in the mesalazine group(P<0.01).Conclusions:The treatment of UC has a clear clinical effect,which indicating that"spleen and stomach weakness,dampness and heat accumulation,qi stagnation and blood stasis" is the key pathogenesis of UC,while "tonifying spleen and stomach,clearing heat and dampness,regulating qi and blood" is an effective method for treating UC.Experimental studies have shown that astragaloside IV may inhibit the expression of ICAM-1 and MMP9,decrease the levels of prion-flammatory cytokines IL?1? and TNF-?,increase the level of anti-inflammatory factor IL-4,regulating the levels of SOD and MDA by inhibiting TLRs/NF-?B signaling pathway.It may be the mechanism of action of astragaloside on UC,and is one of the molecular mechanisms of Qixian Yijiang decoction in the treatment of UC. |
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