Expression of β-catenin in mouse intestinal mucosa siverely dameged by 5-FU
-
摘要:
目的 探讨与肠上皮干细胞增殖关系密切β-catenin 蛋白在5-FU 致小鼠肠黏膜严重损伤时的表达及其意义。 方法取成年C57/BL 小鼠70 只,采用随机数字法将小鼠随机分为对照组(30 只)和实验组(40 只)。实验组予腹腔注射大剂量5-FU[150 mg/(kg·d)×5 d],分别于注射后1、3、5 d每天剖杀10只小鼠,取所有小鼠中段小肠组织固定,进行常规病理组织学检查及免疫化检查肠黏膜中β-catenin蛋白表达情况;对照组腹腔注射等体积的生理盐水,连续注射5 d,处理方法和检测指标与实验组相同。 结果大剂量5-FU作用后,小鼠肠组织受到严重损伤,黏膜炎症、水肿,肠绒毛脱落及肠隐窝消失,随着时间推移,肠黏膜有少量修复;与对照组比较,实验组肠组织β-catenin蛋白表达水平显著增加,随着时间推移,β-catenin蛋白表达阳性的细胞比例逐渐下降。 结论肠黏膜受到损伤后,β-catenin表达增加,促进肠上皮干细胞增殖,完成对肠黏膜的损伤修复。 Abstract:Objective To discusse the expression of β-catenin proten and its significance in mouse intestinal mucosa, and β-catenin was colse related to the proliferation of intestinal stem cells. Methods A total of 70 C57/BL mice were divided two goups randomly, 30 of them were in control group (group A), and other 40 mice were in experimental group. The mice in experimental group were treated with introperitoneal injection of large dose of 5-FU (150 mg/kg body weight for 5 consecutive days), the 30 mice were divied 3 groups, 10 of them were kill at the 1st the 3rd day and the 5th day after the injection was finished. The middle of intestine from these mice was fixed for HE straining and immunohistochemical techniques. The experession of β-catenin in the intestinal sample was detected by immunohistochemical techniques.The mice in control group were introperitoneal injected saline for five days as control, and them were treated as the mice in experimental group. Results After injectin hight dose of 5-FU, the intestine of the mice suffered severe damage: the mucosa was shown as inflammatory oedema, the villi and cryptes disappared, and the mucosa repaired minimally with time. The expression of β-catenin proten in intestianl mucosa of the mice after injecting hight dose of 5-FU increased significantly comparied with control the mice in control group, and percentage of β-catenin proten positive cells in intestinal mucosa gradually decreased with time in mice of experimental group. Conclusion The expression of β-catenin in intestinal mucosa increased when the mice were injected hight dose of 5-FU, meaning the proten could promote the proliferation of intestinal stem cells and finish the regeneration of intestinal mucosa. -
Key words:
- β-catenin /
- 5-FU /
- intestinal stem cells /
- intestinal mucosa
-
表 1 各个时间点实验组与对照组肠年黏膜细胞β-catenin蛋白表达阳性率(n=10)
组别 处理后1 d(%) 处理后3 d(%) 处理后5 d(%) 对照组 2.52±0.45 2.47±0.52 2.55±0.56 实验组 67.34±3.45 52.56±4.74 47.35±0.67 t 值 92.56 81.21 76.45 P 值 <0.01 <0.01 <0.01 -
[1] Dorfman T, Pollak Y, Sohotnik R, et al. Enhanced intestinal epithelial cell proliferation in diabetic rats correlates with β-catenin accumulation[J]. J Endocrinol, 2015, 226(3): 135-43. [2] Lien WH, Fuchs E. Wnt some lose some: transcriptional governance of stem cells by Wnt/β-catenin signaling[J]. Genes Dev, 2014, 28 (14): 1517-32. [3] Zani A, Cananzi M, Fascetti-Leon F, et al. Amniotic fluid stem cells improve survival and enhance repair of damaged intestine in necrotising enterocolitis via a COX-2 dependent mechanism[J]. Gut, 2014, 63(2): 300-9. [4] 罗育其, 吴承堂, 闻英, 等. 大剂量5-FU致肠黏膜严重损伤时肠上皮 msi-1的表达及其意义[J]. 中华普通外科杂志, 2007, 22(12): 939-42. [5] Ogaki S, Shiraki N, Kume K, et al. Wnt and notch signals guide embryonic stem cell differentiation into the intestinal lineages[J]. Stem Cells, 2013, 31(6): 1086-96. [6] 罗育其, 吴承堂, 闻英, 等. 大剂量5-FU致肠黏膜严重损伤时PCNA 的表达[J]. 南方医科大学学报, 2007, 27(12): 1860-2. [7] Krausova M, Korinek V. Wnt signaling in adult intestinal stem cells and cancer[J]. Cell Signal, 2014, 26(3): 570-9. [8] Chen Y, Lee SH, Tsai YH, et al. Ischemic preconditioning increased the intestinal stem cell activities in the intestinal crypts in mice[J]. J Surg Res, 2014, 187(1): 85-93. [9] Sancho R, Cremona CA, Behrens A. Stem cell and progenitor fate in the mammalian intestine: Notch and lateral inhibition in homeostasis and disease[J]. EMBO Rep, 2015, 16(5): 571-81.