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溃疡性结肠炎患者结肠黏膜中的端粒缩短

Telomere shortening in the colonic mucosa of patients with ulcerative colitis.

作者信息

Kinouchi Y, Hiwatashi N, Chida M, Nagashima F, Takagi S, Maekawa H, Toyota T

机构信息

Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.

出版信息

J Gastroenterol. 1998 Jun;33(3):343-8. doi: 10.1007/s005350050094.

DOI:10.1007/s005350050094
PMID:9658312
Abstract

Telomere length in human somatic cells gradually decreases with the number of cell divisions and is regarded as a marker of somatic cell turnover. Mucosal cells of the affected colon show rapid turnover in individuals with active ulcerative colitis (UC). Telomere length was determined by Southern blot analysis of terminal restriction fragments (TRFs) from the colonic mucosa of 17 patients with UC in remission, two of whom showed dysplasia, and 17 control subjects without colitis. For each individual, mean TRF length was compared between rectal mucosa and unaffected cecal mucosa. The mean TRF length of the rectal mucosa was significantly less than that of cecal mucosa in UC patients (7.87 +/- 0.36kb versus 8.77 +/- 0.21 kb; P = 0.0015, Wilcoxon signed rank test), whereas no significant difference was detected in the control subjects. The extent of telomere shortening was 10.6 +/- 3.35% in UC patients, compared with 0.8 +/- 0.64% in noncolitis controls (P = 0.0024, Mann-Whitney U-test). Four UC patients, two of whom had dysplasia, showed telomere shortening of more than 20% in the rectal mucosa. These observations suggest that telomere shortening in the colonic mucosa of individuals with UC may represent the history of mucosal inflammation during disease of long duration, and that it may contribute to aneuploidy in UC.

摘要

人类体细胞中的端粒长度随着细胞分裂次数的增加而逐渐缩短,被视为体细胞更新的一个标志物。在患有活动性溃疡性结肠炎(UC)的个体中,受累结肠的黏膜细胞更新迅速。通过Southern印迹分析测定了17例缓解期UC患者结肠黏膜的末端限制片段(TRF)的端粒长度,其中2例出现发育异常,以及17名无结肠炎的对照受试者的端粒长度。对于每个个体,比较了直肠黏膜和未受累盲肠黏膜的平均TRF长度。UC患者直肠黏膜的平均TRF长度显著短于盲肠黏膜(7.87±0.36kb对8.77±0.21kb;P = 0.0015,Wilcoxon符号秩检验),而在对照受试者中未检测到显著差异。UC患者端粒缩短的程度为10.6±3.35%,而非结肠炎对照为0.8±0.64%(P = 0.0024,Mann-Whitney U检验)。4例UC患者,其中2例有发育异常,其直肠黏膜端粒缩短超过20%。这些观察结果表明,UC患者结肠黏膜中的端粒缩短可能代表了长期疾病过程中黏膜炎症的历史,并且可能导致UC中的非整倍体。

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