摘要
目的研究衰老对于实验性小鼠结肠炎的影响及其可能机制。方法雄性C57BL/6小鼠青年(6～8周)和老年(56周)各10只,各分为对照组和实验组(共4组,每组5只),实验组予葡聚糖硫酸钠(DSS)饮用水,对照组予自由饮用水7 d,第8天处死。采用实时荧光定量PCR检测小鼠结肠组织肿瘤坏死因子(TNF-α)和白细胞介素-6 (IL-6)mRNA相对表达量,电镜观察肠上皮细胞的结构,蛋白电泳和免疫组织化学染色法检测小鼠结肠组织E-cadherin和occlu-din蛋白表达量。结果与青年组比较,老年DSS小鼠体质量下降更明显(t=3. 679,P=0. 006),疾病活动指数更高(t=2. 496,P=0. 037),病理表现更严重(U=0. 000,P=0. 008)及IL-6表达增加(U=4. 000,P=0. 191)。电镜观察老年对照组肠上皮细胞间的紧密连接结构不连续,老年和青年DSS小鼠肠上皮细胞间紧密连接结构模糊,破坏明显。老年实验组小鼠结肠组织E-cadherin (t=0. 184,P=0. 863)和occludin表达(t=0. 399,P=0. 710)低于青年实验组。结论衰老会加重DSS诱发的小鼠结肠炎,其机制可能与衰老相关的肠上皮细胞紧密连接、黏附连接损伤,使肠黏膜屏障功能减退有关。
Objective To explore whether aging increases severity of colitis in mice and its mechanism. Methods Young( 6-8 weeks) and aged( 56 weeks) C57 Bl/6 mice were divided into the control and experimental group( n = 5,each). Dextran sodium sulfate( DSS) was used to induce acute colitis mouse model in the experimental group. The mRNA expressions of tumor necrosis factor-α( TNF-α) and interleukin-6( IL-6) in colon were measured by RT-PCR. Tight junctions( TJs) of intestinal epithelial cells was examined by transmission electron microscopy( TEM). Protein expressions of E-cadherin and occludin were detected by Western blotting and immunohistochemistry in colon. Results Compared with the young DSS-induced mice,the aged DSS-induced mice had more weight loss( t = 3. 679,P = 0. 006),higher disease indexes( t = 2. 496,P =0. 037),higher histologic scores( U = 0. 000,P = 0. 008) and higher colonic IL-6 level( U = 4. 000,P =0. 191). The TJs of intestinal epithelial cells were discontinuous in old healthy rats,and the TJs were destroyed significantly in both young and aged DSS-induced mice. Compared with the young DSS-induced mice,the aged DSS-induced mice had decreased protein expressions of E-cadherin( t = 0. 184,P = 0. 863) and occludin( t =0. 399,P = 0. 710). Conclusions Aging leads to more severe disease following DSS challenge. Age-related deterioration in the functions of the gastrointestinal barrier and integrity may be one of the possible mechanisms.
作者
刘爱玲
汪红英
吕红
钱家鸣
LIU Ailing;WANG Hongying;LU Hong;QIAN Jiaming(Department of Gastroenterology,PUMC Hospital,CAMS and PUMC,Beijing 100730,China;Key Laboratory of Molecular Oncology,Cancer Hospital,CAMS and PUMC,Beijing 100021,China)
出处
《中国医学科学院学报》
CAS
CSCD
北大核心
2019年第1期28-36,共9页
Acta Academiae Medicinae Sinicae
基金
国家卫生计生委公益性行业科研专项(201002020)
中国医学科学院医学与健康科技创新工程(2016-I2M-3-001)
国家自然科学基金(81570505)
2010国家临床重点专科项目
国家科技部973计划(2015CB943203)~~
关键词
衰老
炎症性肠病
紧密连接
肠黏膜屏障
aging
inflammatory bowel disease
tight junction
intestinal barrier
