罗格列酮联合氨基水杨酸治疗溃疡性结肠炎

A clinical trial of rosiglitazone and 5-aminosalicylate combination for ulcerative colitis

目的研究罗格列酮联合5-氨基水杨酸(ASA)对轻、中度活动期溃疡性结肠炎(UC)的疗效及相关细胞因子表达。方法参照2000年全国炎症性肠病学术研讨会制定的对炎症性肠病诊断治疗规范的建议,纳入2004年7-11月四川大学华西医院门诊确诊的慢性轻、中度活动期UC,1个月内未使用激素及免疫抑制剂的病例,排除感染性结肠炎、肠道阿米巴病、心肝肾功能不全者。治疗前后行血粪常规、肝肾功能、结肠镜检查。随机分为治疗组和对照组,均口服5-ASA 2 g／d;治疗组加服罗格列酮4 mg／d,临床观察期4周,4周后乙状结肠镜复查,进行疾病活动度、组织学评价,并观察治疗前后结肠上皮过氧化物酶增殖物激活受体γ(PPARγ)、NF-κB p65的表达。结果UC疾病活动指数积分在治疗组由平均5．87下降到1．86,完全缓解率为71．4％,部分缓解率为23．8％;对照组从6．05下降到2．57,完全缓解率为57．1％,部分缓解率为19．0％。组织学分级下降也高于对照组;PPARγ表达明显增加,NF-κB核阳性率明显降低,且两者之间有相关性。结论罗格列酮与5-ASA或柳氮磺吡啶联合应用较后者单独应用能够提高UC的治疗效果;UC时PPARγ表达降低,PPARγ配体可促进其表达增加;PPARγ缓解结肠炎症可能是通过抑制NF-κB活化完成,并可能代表UC治疗的一个新动向。

Objective To investigate the therapeutic effects of the combination of rosiglitazone, which is peroxisome proliferators-activated receptorγ （PPARγ） ligands used to treat type 2 diabetes mellitus, and aminosalicylate on mildly or moderately active ulcerative colitis and on relevant cytokine expressions. Methods According to the national guideline of China for diagnosis and treatment of the inflammatory bowel disease （IBD）, 42 patients with mild, moderately active ulcerative colitis were selected from the outpatient clinic of West China Hospital from July to November, 2004. Patients with infectious colitis, amoebiasis, or cardiac, renal or hepatic failure were excluded, as well as those who had received corticosteroid or immunosuppressant treatment within the last month. Following a quasi-randomization principle, patients were allocated alternatively into the treatment group with rosiglitazone 4 mg/d plus 5-aminosalicylic acid （5-ASA） 2 g/d or sulfasalazine 3 g/d and the control group with 5-ASA or sulfasalazine alone for 4 weeks. Clinical and histological changes were evaluated weekly by the Mayo scoring system for assessment of the activity of ulcerative colitis and the Truelove-Richards＇ grading system, respectively. PPARγ and nuclear factor （NF）-κB p65 expressions in colonic mucosa were investigated before and after the treatment. Results Mayo scores decreased 4. 01 in treatment group and 3. 48 in control group respectively, with a remission rate 71.4% in treatment group and 57. 1% in control group respectively. Along with the improvement of the Mayo score, the histological grade improvement was more significant in treatment group than in control group （P 〈 0. 05）. PPARγ xpression was higher, and NF-κB p65 positive rate was lower in treatment group than in control group after the treatment, and there was a good negative correlation between PPARγ and NF-κB. Conclusions Combined treatment with rosiglitazone and 5-ASA achieved better therapeutic effect than 5-ASA alone without any side effects. The PPARγ expression was lower in active ulcerative colitis. Rosiglitazone alleviate colonic inflammation probably the through blockade of NF-κB, which can be a novel approach to the ulcerative colitis treatment.