肠黏膜屏障损伤与结肠癌患者恶病质的关系  

Intestinal mucosal barrier damage and the development of cachexia in colon cancer patients

作　　者：黄路桥 姜英健[1] 李畅 张佃良[1] Huang Luqiao, Jiang Yingjian, Li Chang, Zhang Dianliang.(Center of Colon and Rectum, Qingdao Municipal Hospital, Qingdao 266011, Chin)

机构地区：[1]青岛大学医学院附属青岛市市立医院结直肠中心,山东省266011

出　　处：《中华普通外科杂志》2018年第3期235-239,共5页Chinese Journal of General Surgery

基　　金：国家自然科学基金资助项目（81270448、81470890）

摘　　要：目的探讨细菌易位（bacterial translocation，BT）与结肠癌患者恶病质的关系。方法选取2015年9月至2017年5月间青岛市市立医院和南京大学医学院附属金陵医院收治的292例接受右半结肠切除术结肠癌患者的临床资料，分为恶病质组和非恶病质组。采用细菌培养方法检测外周血和肠系膜淋巴结细菌，利用PCR技术检测外周血中细菌DNA，用流式细胞计数法检测肠黏膜T细胞亚群数和NK细胞数，用Western blot和免疫荧光法检测紧密连接蛋白Occludin、Claudins-2、Zonula occluden-2在肠上皮细胞中的表达，用荧光原位杂交检测易位细菌；用免疫组织化学方法检测小肠壁内毒素。结果恶病质组BT率高于非恶病质组（27．8％比7．2％，χ^2=20．871，P〈0．001）。BT（＋）患者肠黏膜中BT与肠上皮细胞中T细胞亚群和NK细胞水平降低有关（CD3^＋T、CD4^＋T、CD8^＋T、CD4^＋T／CD8^＋T、NK细胞水平分别为：36．69％±5．87％比41．63％±5．03％、44．08％±5．12％比49．58％±7．01％、65．68％±5．51％比61．43％±5．58％、0．71％±0．21％比0．91％±0．23％、27．86％±3．93％比34．69％±4．52％，均P〈0．01）。恶病质组BT（＋）患者小肠壁内可以检测到内毒素。在BT（＋）患者中Claudin-2蛋白升高（0．63±0．13比0．21±0．06，t=-2．936，P〈0．01），而Occludin和Zonula occluden-2蛋白降低（0．37±0．13比0．84±0．17，t=2．151，P〈0．05；0．16±0．07比0．58±0．19，t=2．111，P〈0．05）。结论BT可能促进结肠癌患者恶病质的发生，BT可能经肠上皮紧密连接发生。Objective To investigate the association of bacterial translocation （BT） with cachexia in colonic cancer patients. Methods From September 2015 to May 2017 the clinical data of 292 colon cancer patients were studied at Qingdao Municipal Hospital. The bacteria in peripheral blood and mesenteric lymph nodes were detected by bacterial culture, and the bacterial DNA in peripheral blood was detected by PCR technique to determine the occurrence of bacterial translocation. Intestinal epithelial T-cell subsets and NK cells were evaluated using flow cytometry. Western blot and were used to check tight junction proteins Occludin, Claudins-2, Zonula occluden-2 in intestinal epithelium. Fluorescence in situ hybridization and immunohistochemistry were used to detect the translocated bacteria and endotoxin. Results Compared with noncachectic patients, cachectic patients had a significantly higher BT ratio （27.8% vs. 7. 2% ,χ^2 =20. 871 ,P 〈 0. 001 ）. BT in the intestinal mucus layer was associated with lower levels of T-cell subsets and NK cells in the intestinal epithelium in BT（ ± ） patients （ CD3^＋ T： 36. 69% ± 5.87% vs. 41.63% ±5.03%, CD4^＋T： 44.08% ±5.12% vs. 49.58% ±7.01%, CD8^＋T： 65.68% ± 5.51% vs. 61.43% ± 5.58%, CD4^＋T/CD8^＋T： 0.71% ±0.21% vs. 0.91% ± 0.23%, NK： 27. 86% ± 3.93% vs. 34. 69% ± 4. 52% , all P 〈 0.01 ）. Endotoxin was detected within the small intestinal wall in BT （ ＋ ） patients and clandin-2 expression increased （ 0. 63 ± 0. 13 vs. 0. 21 ± 0. 06, t = -2. 936,P 〈0. 01 ）, whereas Oceludin and Zonula occluden-2 expressions decreased（0. 37 ±0. 13 vs. 0.84±0.17,0.16±0.07vs. 0.58±0.19, t=2.151,2.111,bothP〈0.05）. Conclusions BTmay contribute to the development of colon cancer eacheria, and tight junction could be the gateway of BT.

关 键 词：结肠肿瘤 恶病质 紧密连接蛋白质类 细菌易位 

分 类 号：R735.35[医药卫生—肿瘤]