Usselmann B, Newbold M, Morris A G, Nwokolo C U
Department of Gastroenterology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom.
Am J Gastroenterol. 2001 Apr;96(4):1106-12. doi: 10.1111/j.1572-0241.2001.03752.x.
GI epithelial cells express telomerase, a ribonucleoprotein that prevents telomeric shortening in proliferating cells. Telomerase levels are high in cancer, but little is known about telomerase expression in other diseases. We, therefore, designed experiments to determine telomerase expression in different colonic segments and to compare this with corresponding segments in patients with ulcerative colitis. Colorectal cancers and adenomatous polyps were included as disease controls.
In total, telomerase expression was determined in colonic tissues obtained from 62 patients. Twenty-five patients had ulcerative colitis, 21 had normal colons, 11 had colorectal cancer, and nine had adenomatous polyps. Endoscopic biopsies were collected prospectively at colonoscopy, processed for telomerase assays (Telomeric Repeat Amplification Protocol), hematoxylin and eosin staining, and scored for inflammation.
Telomerase activity is expressed in arbitrary units (median 95% confidence interval). In the normal colon, telomerase activity in the cecum, transverse, sigmoid, and rectum was 255 (171-449), 707 (374-895), 561 (468-1426), and 563 (402-846), respectively. Telomerase was higher in the distal three segments when compared with the cecum (p = 0.005). In ulcerative colitis, there was a marked decrease in telomerase activity in the cecum 152 (59-272), p = 0.04, transverse 180 (129-365), p < 0.001, sigmoid 352 (114-464), p = 0.005, and rectum 180 (70-337), p = 0.001 when compared with normals. Telomerase activity correlated negatively with inflammation (r = -0.32, p = 0.001) and was also decreased in microscopically normal areas. Cancers expressed high levels of telomerase.
Colonic mucosal expression of telomerase is reduced in ulcerative colitis. Levels are low even in microscopically normal mucosa, suggesting that telomerase deficiency may contribute to the pathogenesis of the disease.
胃肠道上皮细胞表达端粒酶，这是一种核糖核蛋白，可防止增殖细胞中的端粒缩短。端粒酶水平在癌症中较高，但对于其他疾病中端粒酶的表达了解甚少。因此，我们设计了实验来确定不同结肠段中端粒酶的表达，并将其与溃疡性结肠炎患者的相应结肠段进行比较。将结直肠癌和腺瘤性息肉作为疾病对照。
总共测定了62例患者结肠组织中的端粒酶表达。25例患者患有溃疡性结肠炎，21例患者结肠正常，11例患者患有结直肠癌，9例患者患有腺瘤性息肉。在结肠镜检查时前瞻性收集内镜活检组织，进行端粒酶检测（端粒重复序列扩增法）、苏木精和伊红染色，并对炎症进行评分。
端粒酶活性以任意单位表示（中位数95%置信区间）。在正常结肠中，盲肠、横结肠、乙状结肠和直肠的端粒酶活性分别为255（171 - 449）、707（374 - 895）、561（468 - 1426）和563（402 - 846）。与盲肠相比，远端三个结肠段的端粒酶活性更高（p = 0.005）。在溃疡性结肠炎中，与正常组织相比，盲肠端粒酶活性显著降低至152（59 - 272），p = 0.04，横结肠为180（129 - 365），p < 0.001，乙状结肠为352（114 - 464），p = 0.005，直肠为180（70 - 337），p = 0.001。端粒酶活性与炎症呈负相关（r = -0.32，p = 0.001），并且在显微镜下正常的区域也降低。癌症表达高水平的端粒酶。
溃疡性结肠炎中结肠黏膜端粒酶表达降低。即使在显微镜下正常的黏膜中水平也很低，这表明端粒酶缺乏可能参与了该疾病的发病机制。
