复方苦参汤对溃疡性结肠炎DOR-β-arrestin1-Bcl-2信号转导通路的干预作用  

Intervention effect of Compound Sophorae Flavescentis decoction on DOR-β-arrestin1-Bcl-2 signal transduction pathway in rats with ulcerative colitis

作　　者：范恒[1] 张丽娟[1] 钟敏[1] 刘星星[1] 段雪云[2] 左冬梅[1] 唐庆[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院中西医结合科,湖北省武汉市430022 [2]湖北中医药大学附属医院药剂科,湖北省武汉市430061

出　　处：《世界华人消化杂志》2013年第8期647-654,共8页World Chinese Journal of Digestology

基　　金：国家自然科学基金资助项目;No.81072944~~

摘　　要：目的:探讨复方苦参汤对溃疡性结肠炎大鼠DOR-β-arrestin1-Bcl-2信号转导通路的干预作用.方法:SD♂大鼠84只(体质量200g±20g)随机分为空白对照组、模型组、美沙拉嗪组、复方苦参汤大剂量组、复方苦参汤中剂量组和复方苦参汤小剂量组,每组14只.除对照组外,其余5组均依据Morris等三硝基苯磺酸(trinitrobenzene sulfonic acid,TNBS)建立大鼠溃疡性结肠炎模型.造模后观察记录大鼠的大便和精神状态,并于第3天随机处死2只造模大鼠,取结肠镜下观察其病理组织学变化发现:大鼠结肠糜烂、充血及溃疡,证明造模成功.建立大鼠溃疡性结肠炎模型后给予美沙拉嗪组大鼠3mL/d(0.5g/L)美沙拉嗪混悬液灌胃,复方苦参汤大、中、小剂量组分别按不同含生药浓度的复方苦参汤液3mL/d(0.67、0.34、0.17g/L)灌胃,对照组和模型组给予等量的生理盐水3mL/d灌胃,连续灌胃15d后,禁食24h,处死大鼠,取结肠组织石蜡包埋切片,HE染色比较各组结肠组织病理组织学改变,Realtime-PCR和免疫组织化学技术检测实验大鼠结肠组织的Bcl-2、β-arrestin1及δ阿片受体(delta opioid receptor,DOR)mRNA和蛋白表达表达变化.结果:各组大鼠结肠组织中Bcl-2、β-arrestin1和DOR表达有显著差异(P<0.05).与对照组比较,模型组的大鼠结肠黏膜组织Bcl-2、β-arrestin1和DOR表达明显升高(24.11±12.61vs11.88±5.90,38.90±5.30vs14.34±8.97,23.57±9.96vs9.68±3.94,均P<0.05);与模型组比较,美沙拉嗪组和复方苦参汤大、中、小剂量组的大鼠结肠黏膜组织Bcl-2、β-arrestin1、DOR表达均显著下降,但美沙拉嗪组和复方苦参汤大、中、小剂量组之间比较Bcl-2、β-arrestin1、DOR表达无显著差异.结论:在实验性溃疡性结肠炎大鼠结肠组织中DOR、β-arrestin1和Bcl-2的表达升高,DOR-β-arrestin1-Bcl-2信号转导通路可能参与了溃疡性结肠炎的病理过程,复方苦参汤可改善溃疡性结肠炎大鼠的结肠组织病理�AIM To explore the intervention effect of Com- pound Sophorae Flavescentis decoction on the DOR-β-arrestinl-Bcl-2 signal transduction path- way in rats with ulcerative colitis. METHODS： Eighty-four Sprague-Dawley rats were equally and randomly divided into normal control group, model group, mesalazine group, high-, medium-, and low-dose Compound So- phorae Flavescentis decoction groups, Except for the normal control group, ulcerative colitis was induced with trinitrobenzene sulfonic acid （TNBS） in rats of other groups. After induction of ulcerative colitis, bloody stools, mental state and diarrhea were observed and recorded daily. Two rats in the model group were randomly se- lected and executed on day 3 for observing path- ological changes in the colon tissue. Rats in the mesalazine group and Compound Sophorae Fla- vescentis decoction groups were lavaged with mesalazine solution and Compound Sophorae Flavescentis decoction for 15 d, while those in the normal control group and model group were given equal volume of distilled water for the same duration. On day 16, the remaining rats were executed to detect histopathological chang- es in the colon tissue and the mRNA and protein expression of DOR, β-arrestinl and Bcl-2 in the colon tissue by real-time PCR and immunohisto- chemistry, respectively. RESULTS： The mRNA and protein expression of DOR, β-arrestinl and Bcl-2 differed signifi- cantly among each group （P 〈 0.05）. Compared to the normal control group, the mRNA and protein expression of DOR, β-arrestinl and Bcl-2 protein was significantly increased （24.11 ± 12.61 vs 11.88 ± 5.90, 38.90 ±5.30 vs 14.34 ± 8.97, 23.57 ± 9.96 vs 9.68± 3.94, all P 〈 0.05） in the colon mucosa in the model group. Compared to the model group, the mRNA and protein expression of DOR, β-arrestinl and Bcl-2 in the colon muco- sa was significantly decreased in the mesalazine group and Compound Sophorae Flavescentis decoction groups; however, the mRNA and pro- tein expression of DOR, β-arrestinl and Bcl-2 did

关 键 词：Δ阿片受体 β-arrestin1 Bcl-2 信号转导通路 溃疡性结肠炎 复方苦参汤 

分 类 号：R285.5[医药卫生—中药学]