酒精通过抑制肠上皮干细胞增殖损伤肠上皮的更新修复能力

doi:10.3969/j.issn.1672-5069.2020.03.004

摘要/Abstract

摘要： 目的研究酒精对肠上皮干细胞(ISC)和肠上皮更新修复能力的影响。方法将18只C57BL/6小鼠随机分为对照组(n=9)和酒精处理组(n=9)。采用Gao-Binge法制备慢性酒精中毒模型。在造模成功后,腹腔注射5-溴-2-脱氧脲苷(BrdU),分别在注射后2 h、24 h和72 h取小肠组织,采用免疫组化法检测BrdU阳性细胞和ISC特异性标志物Lgr5表达。结果与对照组小鼠比,酒精处理组小鼠小肠绒毛高度显著缩短、萎缩;酒精处理组小鼠ISC细胞Lgr5表达显著弱于对照组;酒精处理组小鼠每个肠隐窝BrdU阳性细胞数量为(3.50±0.65)个/肠隐窝,显著少于对照组【(7.90±1.08)个/肠隐窝,P＜0.05】;在注射BrdU 后2 h、24 h和72 h,酒精处理组小鼠小肠BrdU阳性细胞迁移距离分别为(66.67±1.60)μm、(219.40±12.11)μm和(313.90±9.76)μm,显著短于对照组【分别为(111.10±1.60)μm、(319.00±10.04)μm和(625.90±3.34)μm,P＜0.05】。结论酒精通过抑制ISC引起肠上皮细胞增殖和迁移能力下降,从而损伤肠上皮的更新修复能力,导致肠上皮屏障功能障碍。

关键词: 肠上皮干细胞, 酒精, 增殖, 小鼠 , ,

Abstract: Objective The aim of this experiment was to explore the effect of alcohol on intestinal stem cell proliferation. Methods 18 C57BL/6 mice were randomly divided into control and alcohol group (9 in each). A mouse model with chronic alcohol injury was established by Gao-Binge method. Before sampling, the 5-bromo-2′-deoxyuridine (BrdU) was intraperitoneally injected. At 2 h, 24 h and 72 h after BrdU injection, the small intestine tissues were collected and immunohistochemical staining was conducted to detect BrdU positive cells. The number of BrdU positive cells in small intestinal tissue at 2 h was used as the detection index of intestinal epithelial cell proliferation, and the distances of BrdU positive cells from the distal end of small intestinal villi to the basal part of small intestinal crypt at 2 h, 24 h and 72 h were dynamically measured as the detection index of intestinal epithelial cell migration. The expression of intestinal stem cell specific marker, Lgr5 was detected by immunohistochemistry. Results The small intestinal villi in alcohol-intervened group were significantly shortened and atrophic compared with those in the control group; the expression of Lgr5 in alcohol-intervened group was significantly weaker than that in control group; the number of BrdU positive cells in each intestinal crypt in experimental group was (3.50±0.65), significantly less than that in control group ; the migration distance of BrdU positive cells in alcohol-intervened group at 2 h, 24 h and 72 h after BrdU injection were (66.67±1.60) μm, (219.40±12.11) μm and (313.90±9.76) μm, significantly shorter than those in the control . Conclusion Alcohol induces decreased proliferation and migration of intestinal epithelial cells by inhibiting intestinal stem cell proliferation, which might damage the renewal and repair ability of intestinal epithelium, leading to abnormal intestinal epithelial barrier functions.

Key words: Alcohol, Intestinal stem cell, Proliferation, Mice

王洪岩,徐有青,李鑫,徐睿玲,郭淑媛,付红梅,闫朝岐. 酒精通过抑制肠上皮干细胞增殖损伤肠上皮的更新修复能力[J]. 实用肝脏病杂志, 2020, 23(3): 316-319.

Wang Hongyan, Xu Youqing, Li Xin, et al.. Alcohol damages intestinal epithelial renewal and repair by inhibiting intestinal stem cell proliferation[J]. Journal of Practical Hepatology, 2020, 23(3): 316-319.

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