阿螺旋霉素在急性小鼠溃疡性结肠炎模型中的保护性作用  

17-DMAG protects mice from dextran sulphate sodium induced acute ulcerative colitis

作　　者：吴琳[1] 汪芳裕[1] 路又可[1] 刘炯[1] 陆恒[1] 刘畅[1] 陈春燕[1] 李楠[1] 陶慧[1] 

机构地区：[1]中国人民解放军南京军区南京总医院消化内科,江苏省南京市210002

出　　处：《世界华人消化杂志》2014年第7期975-981,共7页World Chinese Journal of Digestology

基　　金：国家自然科学基金资助项目;No.81270453~~

摘　　要：目的:研究阿螺旋霉素[17-(dimethylaminoethylamino)-17-demethoxygeldanamycin hydrochloride,17-DMAG]在葡聚糖硫酸钠(dextran sulphate sodium,DSS)诱导的小鼠溃疡性结肠炎治疗中的作用.方法:C57BL/6小鼠随机分为正常对照组、DSS模型组、磷酸盐缓冲液(phosphate buffer,P B S)治疗组以及17-D M A G治疗组.采用3%D S S连续饮入以复制溃疡性结肠炎小鼠模型.对结肠炎模型小鼠每日腹腔注射17-DMAG[10 mg/(kg?d)]或同体积PBS.观察小鼠体质量、疾病活动度、单位长度结肠质量、结肠病理损伤程度及结肠上皮细胞凋亡情况,以评价17-DMAG对小鼠溃疡性结肠炎病程发展的影响.结果:3%DSS连续饮入5 d后,模型组小鼠较正常对照组小鼠体质量减轻,疾病活动度、单位肠道结肠重量、结肠病理评分及结肠上皮细胞凋亡增加.与PBS治疗组相比,17-DMAG治疗5 d后,结肠炎小鼠体质量降低程度(90.9%±7.78%vs 81%±5.44%,P<0.05)及疾病活动度显著改善(1.8±0.84 vs 4.7±1.21,P<0.05),单位长度结肠质量(4.43 mg/mm±0.16 mg/mm vs 5.71 mg/mm±0.56 mg/mm,P<0.01)及结肠病理评分降低(4.6±1.30 vs 7.4±0.30,P<0.01),结肠上皮细胞凋亡数目(33.2±5.50vs 62.6±9.81,P<0.01)显著减少.结论:17-DMAG可减轻DSS诱导的小鼠溃疡性结肠炎,其可能通过抑制结肠上皮细胞的凋亡而发挥作用.AIM： To investigate the potential effect of alvespimycin [17-（dimethylaminoethylamino）-17-demethoxygeldanamycin hydrochloride, 17-DMAG）], a novel water soluble heat shock protein 90（HSP90） inhibitor, in the treatment of dextran sulphate sodium（DSS） induced murine ulcerative colitis. METHODS： C57BL/6 mice were randomly assigned to a normal control group, a colitis model group, a PBS treatment group and a 17-DMAG treatment group. Phosphate buffered solution （PBS） or 17-DMAG was given daily by intraperitoneal injection. Acute ulcerative colitis was induced by administering ad libitum 3%DSS in the drinking water for 5 days. Body weight, diarrhea and bleeding scores were determined daily to calculate the disease activity index. Five days later, the mice were sacrificed and colon tissues were collected. Colon length and weight, histological score of colon injury, and apoptotic index of colon epithelial cells were detected to assess the effects of 17-DMAG on the development of DSS induced colitis. RESULTS： Mice receiving 3% DSS showed significantly reduced body weight, increased disease activity index, colon weight/length ratio, histological score and apoptotic index of colon epithelial cells, compared with controls. Compared with colitis mice treated with PBS, daily intraperitoneal injection of 17-DMAG for 5 d significantly ameliorated body weight loss（90.9 ± 7.78 vs 81 ± 5.44, P〈0.05）, significantly decreased disease activity index（1.8 ± 0.84 vs 4.7 ± 1.21, P〈0.05）, colon length and weight（4.43 mg/mL ± 0.16 mg/mL vs 5.71 mg/mL ± 0.56 mg/mL, P〈0.01）, and histological score（4.6 ± 1.30 vs 7.4 ± 0.30, P〈0.01）. Most importantly, 17-DMAG treated mice showed obviously decreased apoptotic index of colon epithelial cells（33.2 ± 5.50 vs 62.6 ± 9.81, P〈0.01） than PBS treated mice. CONCLUSION： Daily intraperitoneal injection of 17-DMAG attenuated DSS induced acute murine ulcerative colitis possibly by inhibiting apoptosis of colon epithelial cells.

关 键 词：炎症性肠病 溃疡性结肠炎 热休克蛋白90 阿螺旋霉素 

分 类 号：R574.62[医药卫生—消化系统]