van Gorkom B A, Karrenbeld A, van Der Sluis T, Koudstaal J, de Vries E G, Kleibeuker J H
Department of Gastroenterology and Hepatology, University Hospital, Groningen, The Netherlands.
Digestion. 2000;61(2):113-20. doi: 10.1159/000007743.
Chronic use of sennoside laxatives often causes pseudomelanosis coli. A recent study suggested that pseudomelanosis coli is associated with an increased colorectal cancer risk. A single high dose of highly purified senna extract increased proliferation rate and reduced crypt length in the sigmoid colon compared to historical controls.
To evaluate in a controlled study the effects of highly purified senna extract on cell proliferation and crypt length in the entire colon and on p53 and bcl-2 expression.
Addition of a senna extract to colonic lavage was studied in 184 consecutive outpatients. From 32 randomised patients, 15 with sennosides (Sen), 17 without (NSen), biopsies were taken. Proliferative activity was studied in 4 areas of the colon, using 5-bromo-2'-deoxyuridine labelling and immunohistochemistry (labelling index, LI). Expression of p53 and bcl-2 in the sigmoid colon was determined immunohistochemically.
Crypts were shorter in Sen than in NSen in the transverse and sigmoid colon. LI was higher in Sen than in NSen in the entire colon. No difference in p53 expression was seen. Bcl-2 expression was higher in both groups when crypts were shorter and/or proliferation was increased.
Sennosides induce acute massive cell loss probably by apoptosis, causing shorter crypts, and increased cell proliferation and inhibition of apoptosis to restore cellularity. These effects may reflect the mechanism for the suggested cancer-promoting effect of chronic sennoside use.
长期使用番泻苷类泻药常导致结肠黑变病。最近一项研究表明，结肠黑变病与结直肠癌风险增加有关。与历史对照相比，单次高剂量的高纯度番泻叶提取物可增加乙状结肠的增殖率并缩短隐窝长度。
在一项对照研究中评估高纯度番泻叶提取物对整个结肠细胞增殖、隐窝长度以及p53和bcl-2表达的影响。
对184例连续门诊患者进行了在结肠灌洗中添加番泻叶提取物的研究。从32例随机分组的患者中，15例使用番泻苷（Sen组），17例未使用（非Sen组），均进行了活检。使用5-溴-2'-脱氧尿苷标记和免疫组织化学（标记指数，LI）在结肠的4个区域研究增殖活性。通过免疫组织化学法测定乙状结肠中p53和bcl-2的表达。
在横结肠和乙状结肠中，Sen组的隐窝比非Sen组短。在整个结肠中，Sen组的LI高于非Sen组。p53表达未见差异。当隐窝较短和/或增殖增加时，两组的bcl-2表达均较高。
番泻苷可能通过凋亡诱导急性大量细胞丢失，导致隐窝变短，细胞增殖增加并抑制凋亡以恢复细胞数量。这些作用可能反映了长期使用番泻苷类泻药所提示的促癌作用机制。
