Clinical Analysis Of Patients With Ulcerative Colitis And Their Clinicopathological Study Of The Expression Of TGF β1 Signalling Pathway Proteins

Background and objective Ulcerative colitis(UC) is a chronic inflammatory disease with unknown aetiology.It is difficult to be cured completely for its recurrent attacks.Analysing the clinical characters of hospitalized patients with ulcerative colitis is beneficial to improve the level of diagnose and cure and the patients' quality of life. Although its pathogenesy remains unclear,there is evidence that chronic intestinal inflammation is caused by an excessive immune response to mucosal antigens and inappropriately controlled by the normal counter regulatory mechanisms.The increase of pro-inflammatory cytokines and the decrease of anti-inflammatory cytokines play a major role in the dysregulated immune response and chronic intestinal inflammatory. Both in vitro and in vivo studies have demonstrated that TGF-β1 acts as a potent negative regulator of mucosal inflammation.With the investigation of Smads protein family,it has been shown that the abnormal expression of Smads by which TGF-β-triggered signals are transduced may contribute to intestinal inflammation.This research,by retrospective studying the hospitalized patients with ulcerative colitis,was to explore the clinical characters and the corresponding colonoscopy detection rate.At the same time,the correlation of the expression level and clinical stage,extent of disease and the histological grade was explored by studying the expressions of TGF-β1,TGFβRⅠ,Smad3 and Smad7 in the tissues of UC,which was expected to explore the aetiology and pathogenesy of UC and find new biological markcrs to evaluate the disease activity of ulcerative colitis and a beneficial way to treat UC wonderfully. Methods The data of 120 cases of UC were obtained from three hospitals in Lu'an city of Anhui province from 2000 to 2006.The patients were registed according to case questionnaire of UC.The clinical characters,treatment,hospitalization and the corresponding colonoscopy detection rate were reviewed.In which,the tissue samples of 38 cases of active stage and 22 cases of clinical remission in UC were collected from. 16 normal colonic mucosa specimens of IBS or colonic polyp were taken as control group.The samples were routinely fixed in 10%formalin and embedded in paraffin. After sectioned into slices,we detected the expression of TGF-β1,TGFβRⅠ,Smad3 and Smad7 protein by immunohistochemical staining technique(SABC method).We analyzed the relationship between the expression of TGF-β1,TGFβRⅠ,Smad3 and Smad7 protein with clinical and pathologic parameters.Results(1) Clinical Analysis of UC:Of 120 patients,74 men,36 women,the ratio of male/female is 1.61:1,and the mean age were 42.5±14.4 years.There is significance difference between male and female.The peak years of invasive age are during the period from 30 to 39 years.Most of the hospitalized UC patients revealed mild(42.5%) or moderate severity(30.8%).In all cases,65.8%were first onset,26.7%were chronic relapsing.The major symptoms were diarrhea(98.35%),bloody stool(95.8%) and abdominal pain(89.2%).About 2.5%of UC patients had extraintestinal manifestations, and 3.3%had complications.Among UC patients,75.0%was colitis of left-colon. The mainstay for UC treatment was 5-aminosalicylate(68.3%) and glucocorticoids (31.7%),and the therapeutic effect was well.The remission rate by medicine reached 97.5%.The mortality was 0.8%(1 case).There has been an increasing number of hospitalized UC and colonoscopy detection rate in recent years.(2) Expression of TGF 81 Signalling Pathway Proteins in UC:The expression of TGF-β1 and TGFβRⅠin UC was significantly higher than that in control groups,and the expression in activc discase was also significantly higher than that in clinical remission.Furthermore,there was positive correlation between the expression level and histological grade(r=0.421 and 0.553,P＜0.05).The expression of Smad3 in UC was significantly lower than that in control groups(P＜0.05),but there was no difference between active disease and clinical remission(P＞0.05).There was negative correlation between the expression level of Smad3 and histological grade(r=-0.283,P＜0.05).The expression of Smad7 in UC was significantly higher than that in control groups,and the expression in active disease was also significantly higher than that in clinical remission.There was negative correlation between the expression level of Smad3 and Smad7(r=-0.420,P＜0.05).The expression level of TGF-β1,TGFβRⅠ,Smad3 and Smad7 in UC had no correlation with extent of disease(r=0.438,P＞0.05).Conclusion(1) There has been an increasing number of hospitalized UC in recent years,mostly with mild to moderate severity.There is few case of UC with extraintestinal manifestations and complications.The treatment with SASP/5-ASA or steroids for patients has acquired excellent therapeutic effect.However,the compliance of patients out of hospital is not so well.Therefore,the relapse rate was high among those patients.(2) The high expression of TGFβ1,TβRⅠand Smad7 and the low expression of Smad3 in UC show that the abnormal expression of TGFβ1 signalling pathway proteins are correlated with the pathogenesy of UC.Furthermore,TGFβ1,TβRⅠ,Smad3 and Smad7 may serve as disease activity markers of ulcerative colitis.