摘要
目的:探讨COX-2、PPARγ和NF-κB p65在溃疡性结肠炎(UC)发病机制中的作用及相互关系.方法:选择华西医院消化科确诊的32例UC患者和26例健康体检者或结肠单发息肉切除术后复查肠镜检查正常者,按Baron评分标准进行内镜分级;按Riley-Mani-goodman分类方法进行病理学分级.采用免疫组织化学SP法检测活动期溃疡性结肠炎内镜活检标本和正常对照石蜡包埋组织中COX-2、PPARγ和NF-κB p65的表达情况.结果:32例UC患者按Riley-Mani-goodman方法进行病理学分级Ⅰ级19例,Ⅱ级9例,Ⅲ级4例.UC组结肠黏膜炎症组织COX-2、NF-κBp65蛋白均为阳性表达,主要分布于上皮细胞,固有层炎性细胞,对照组为阴性或弱阳性表达.二者在UC炎症组织表达高于正常对照组(P<0.05);PPARγ主要表达于结肠上皮细胞的细胞质中,在UC炎症组织表达低于正常对照组(P<0.05).三者在UC组的表达与对照组相比,差异均有非常显著性(P<0.01).COX-2蛋白表达与病理分级无相关;PPARγ蛋白表达与病理分级之间有负相关(H=411,P<0.05).NF-κBp65蛋白表达与病理分级之间存在正相关(H=16.77,P<0.01).COX-2与NF-κB p65蛋白表达正相关(r=0.92,P<0.01),NF-κBp65与PPARγ蛋白表达负相关(r=0.905,P<0.01).结论:NF-κB的诱导参与UC的发生发展,COX-2,PPARγ也参与UC的炎症及损伤过程,COX-2可能通过作用于PPARγ-NF-κB p65信号传导通路,而影响UC炎症的发生发展.COX-2、PPARγ、NF-κB可能作为治疗UC的靶位,在UC治疗中具有重要意义.
AIM：To investigate the significance of cyclooxygenase-2 COX-2）,peroxisome proliferatoractivated receptorγ（PPARγ）,and nuclear transcription factor-kappa B（NF-κB）p65 expression in ulcerative colitis（UC）and to analyze their correlation.METHODS：The colonic biopsies were collected from 32 UC patients and 26 healthy controls at West China Hospital.The endoscopic grades of UC were assessed according to the Baron Scale.The pathological grades of UC were classified according to the Riley-Mani-Goodman classification.The expression of COX-2,PPARγand NFκB P65 proteins in colonic mucosa was determined by immunohistochemistry.RESULTS：According to Riley-Mani-Goodman classification,19 UC patients had grade I disease,9 had grade II disease,and 4 had grade III disease.COX-2 and NF-κB p65 proteins were mainly distributed in epithelial cells and lamina propria inflammatory cells in UC,but were negatively or weakly expressed in normal colonic mucosa.The expression levels of COX-2 and NF-κB p65 proteins in UC patients were significantly higher than those in healthy controls（both P0.05）.PPARγwas mainly expressed in the cytoplasm of colonic epithelial cells.The expression of PPARγprotein in UC patients was significantly lower than that in healthy controls（P 0.05）.Although the expression of COX-2 protein was not correlated with the histological grade of UC,a good correlation between the expression of PPARγand NF-κB p65 and histological grade was noted（H=411,P0.05;H=16.77,P0.01）.There is a positive correlation between COX-2 and NF-κB p65 protein expression in UC（r=0.92,P0.01）,while a negative correlation was found between NF-κB P65 and PPARγprotein expression（r=0.905,P0.01）.CONCLUSION：NF-κB expression is involved in the development and progression of UC.COX-2 and PPARγare also involved in the process of inflammation/injury in UC.COX-2 affects the process of inflammation in UC possibly by acting upon the PPARγ-NF-κB p65 signaling pathway.COX-2,PPARγand NF-κB p65 may be used as targets for UC therapy.
出处
《世界华人消化杂志》
CAS
北大核心
2010年第25期2660-2665,共6页
World Chinese Journal of Digestology
