Gibson P, Rosella O, Nov R, Young G
University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Victoria, Australia.
Gut. 1995 Jun;36(6):857-63. doi: 10.1136/gut.36.6.857.
The hypothesis that the colonic epithelium is diffusely abnormal in ulcerative colitis was examined by comparing disease related responses in expression of markers of differentiation by colonic crypt cells to culture with and without butyrate. Cells were isolated from patients with normal colon (15), cancer (24), ulcerative colitis (19), or Crohn's disease (16). Alkaline phosphatase activities were measured in cell homogenates and the rate of glycoprotein synthesis assessed at the end of 24 hours of culture and expressed relative to the rate of protein synthesis as the G:P ratio. Alkaline phosphatase activities, but not G:P ratios, differed across the groups before and after 24 hour culture (p < 0.05), activities being lowest in the cancer group and highest in inflammatory bowel disease groups. Butyrate (1 mM) suppressed alkaline phosphatase activities in the cancer group by mean (SEM) of 17 (4) (p = 0.006) compared with no change in the other groups. Butyrate suppressed G:P ratios only in the cancer (6 (3)%, p = 0.03) and ulcerative colitis groups (5 (3)%, p = 0.04) and the changes in both were different (p < 0.05) from those in normal cells (increase of 10 (7)%). Changes in ulcerative colitis were different from those in Crohn's disease (p = 0.029). Responses were independent of the presence or absence of mucosal inflammation. These data confirm the diffuse nature of epithelial abnormalities in colorectal cancer. In ulcerative colitis, a different pattern of abnormality occurs, supporting the notion that the epithelium is also diffusely abnormal independent of mucosal inflammation.
通过比较结肠隐窝细胞在添加和不添加丁酸盐培养时分化标志物表达的疾病相关反应，来检验溃疡性结肠炎中结肠上皮弥漫性异常这一假说。从正常结肠患者（15例）、癌症患者（24例）、溃疡性结肠炎患者（19例）或克罗恩病患者（16例）中分离细胞。测定细胞匀浆中的碱性磷酸酶活性，并在培养24小时结束时评估糖蛋白合成速率，以相对于蛋白质合成速率的G:P比值表示。培养24小时前后，各组间碱性磷酸酶活性存在差异（p<0.05），而G:P比值无差异，癌症组活性最低，炎症性肠病组活性最高。与其他组无变化相比，丁酸盐（1 mM）使癌症组碱性磷酸酶活性平均（SEM）降低17（4）（p = 0.006）。丁酸盐仅使癌症组（6（3）%，p = 0.03）和溃疡性结肠炎组（5（3）%，p = 0.04）的G:P比值降低，且两者变化与正常细胞（升高10（7）%）不同（p<0.05）。溃疡性结肠炎的变化与克罗恩病不同（p = 0.029）。这些反应与黏膜炎症的有无无关。这些数据证实了结直肠癌上皮异常的弥漫性。在溃疡性结肠炎中，出现了不同的异常模式，支持了上皮也独立于黏膜炎症而弥漫性异常的观点。
