The Mechanism Of Anti-ulcerative Colitis Was Studied Based On IL-6/JAK/STAT3 Pathway

Object:To establish the rat model of ulcerative colitis using 2,4,6 three trinitrobenzene sulfonic acid-ethanol composite method,to study the therapeutic effect of Gallnut aqueous extract on rat model of ulcerative colitis and its anti-ulcerative mechanism from antioxidant and anti-inflammatory cytokines and colon tissue UC gene and protein expression.Method:(1)Establishment of rat ulcerative colitis model by 2,4,6 three nitrobenzene sulfonic acid ethanol combined method.(2)general observation and weight change were used to evaluate the therapeutic effect of normal group,model group and each drug delivery group on UC rats.(3)The expression level of IL-6?IL-10?TNF-??PGE2 and other cell factors in serum of UC rats was detected by ELISA.(4)The activity of SOD and MDA in serum of UC rats was determined by hydroxylamine method and TBA method.(5)The expression of JAK protein in serum of UC rats was determined by ELISA(enzyme-linked immunosorbent assay).(6)The effect of the Gallnut aqueous extract on the reverse transcriptase level of STAT3?IL-6 and TNF-? in UC rats was detected by RT-PCR method.Results:(1)Compared with the normal group,model group,the number of white blood cells increased(P<0.01);Compared with the model group,positive control group,Gallnut aqueous extract of low dose and high dose group decreased the number of peripheral white blood cell(P<0.05),Gallnut aqueous extract compound group low dose group of peripheral white blood cells decreased(P<0.05);(2)Compared with the normal control group,model group increased TNF-??PGE2?IL-6 level,lower the level of IL-10(P<0.05);compared with the model group,positive control group,Gallnut aqueous extract low dose and high dose group of lower the TNF-??PGE2 and IL-6 level,increased the level of IL-10(P<0.05),Gallnut aqueous extract compound high dose group of lower the TNF-??PGE2 and IL-6level,increased the level of IL-10(P<0.05).(3)Compared with the normal group,the level of SOD in the model group decreased and the level of MDA increased(P<0.01).Compared with model group,SOD level increased and MDA level decreased in positive control group,Gallnut aqueous extract low and high dose group(P<0.05),SOD level in Gallnut aqueous extract compound group increased,and MDA level in Gallnut aqueous extract group decreased(P<0.05).(4)Compared with the normal group,the expression of JAK protein in the model group was higher than that in the model group(P<0.01).Compared with the model group,the expression of JAK protein in the positive control group and the high dose group of Gallnut aqueous extract decreased,while the expression of JAK protein in the Gallnut aqueous extract compound group decreased(P<0.05).(5)Compared with the control group,model group,TNF-??IL-6 and STAT3 expression is increased(P<0.01);Compared with the model group,positive control group,Gallnut aqueous extract high dose group IL-6 expression is reduced,Gallnut aqueous extract low and high dose group of TNF-??STAT3 expression is reduced,Gallnut aqueous extract compound high dose group IL-6?TNF-? expression was decreased(P<0.05).Conclusion: Gallnut aqueous extract could promote the healing of ulcer tissue of ulcerative colitis rat model,significantly improve the pathological lesion of colon in rats with UC structure can reduce UC rat blood WBC? IL-6?PGE2?TNF-??MDA level,increased SOD and IL-10 levels,obviously have anti-inflammatory and antioxidant injury;The mechanism by reducing serum IL-6?TNF-? levels and the ulcer tissue IL-6?TNF-? gene expression,thereby reducing the expression of JAK protein decreased the phosphorylation of STAT3 and expression of STAT3 gene,the multiple target plays an important role in anti-ulcerative colitis.