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当前位置: 首页 > 文章 > 甲氨蝶呤通过抑制Wnt/β-catenin信号通路诱导小鼠肠道损伤 饲料工业 2019 (1) 34-40
Position: Home > Articles > Methotrexate induces intestinal injury by inhibiting Wnt/β-catenin signaling pathway in mice Feed Industry 2019 (1) 34-40

甲氨蝶呤通过抑制Wnt/β-catenin信号通路诱导小鼠肠道损伤

作  者：
黄登桂;周加义;秦颖超;王修启
单  位：
华南农业大学动物科学学院广东省动物营养调控重点实验室国家生猪种业工程技术研究中心
关键词：
甲氨蝶呤;肠道;Wnt/β-catenin信号通路;增殖;屏障功能;小鼠;CMT-93细胞
摘  要：
研究旨在探讨甲氨蝶呤(methotrexate, MTX)对小鼠肠上皮更新的影响及其机理。选用体重相近的5～6周龄的昆明小鼠64只,随机分为两组,每组设32个重复,每个重复1只小鼠,连续2 d分别腹腔注射生理盐水和50 mg/kg BW MTX溶液,并于注射后72 h处死小鼠;同时用0.025、0.05、0.10μM和0.20μM MTX处理小鼠结肠癌细胞系CMT-93。结果表明,MTX可显著降低小鼠平均日采食量、日饮水量和日增重(P<0.05);显著降低十二指肠、空肠和回肠肠重(P<0.05),其中空肠肠重降低幅度最大,达到28.14%;MTX导致小鼠空肠绒毛顶部上皮细胞脱落,绒毛高度显著降低(P<0.05),固有层裸露,隐窝增生明显,隐窝深度显著增加(P<0.05),绒毛高度/隐窝深度比值显著降低(P<0.05);空肠中ZO-1、Occludin、β-catenin和PCNA蛋白质表达显著降低(P<0.05),Caspase-3蛋白质表达显著增加(P<0.05);0.025、0.05、0.10μM和0.20μM MTX处理CMT-93细胞24 h即可显著抑制其增殖活性(P<0.05),且抑制效果呈剂量依赖性;0.025μM和0.05μM MTX显著降低CMT-93细胞跨膜电阻值(P<0.05)和ZO-1、Occludin、β-catenin、PCNA蛋白质表达(P<0.05),增加Caspase-3蛋白质表达。结果提示,MTX降低Wnt/β-catenin信号通路活性,抑制肠上皮细胞增殖,促进其凋亡,破坏肠道屏障功能,诱导肠道结构损伤。
译  名：
Methotrexate induces intestinal injury by inhibiting Wnt/β-catenin signaling pathway in mice
作  者：
Huang Denggui;Zhou Jiayi;Qin Yingchao;Wang Xiuqi;
单  位：
Huang Denggui%Zhou Jiayi%Qin Yingchao%Wang Xiuqi
关键词：
methotrexate;;intestine;;Wnt/β-catenin signaling pathway;;proliferation;;barrier function;;mice;;CMT-93 cell
摘  要：
This experiment was conducted to study the effect of methotrexate(MTX)on intestinal epithelial regeneration of KM mice.Sixty-four similar age and body weight healthy KM mice were selected and randomly assigned to two groups with thirty-two replicates and one mouse with each pen.The mice of two groups were injected with the normal saline and MTX solution with 50 mg/kg BW respectively,and were killed at 72 h after injection.Meanwhile,CMT-93 cells were treated with 0.025,0.05,0.10μM and 0.20μM MTX.The results showed that(1)MTX decreased the average daily feed intake(ADFI),average daily water intake(ADWI)and average daily gain(ADG)significantly(P<0.05);(2)MTX reduced weight of the intestine(duodenum,jejunum and ileum)significantly(P<0.05),and the weight of jejunum reduced most significantly(28.14%);(3)MTX decreased(P<0.05)villus height(VH),increased(P<0.05)crypt depth(CD),reduce(P<0.05)ratio of villus height/crypt depth(V/C);(4)MTX value(P<0.05)and the expression of ZO-1,Occludin,β-catenin and PCNA(P<0.05),and increased the expression of Caspase-3 protein in CMT-93 cells(P<0.05).These results indicated that MTX could decrease the activity of Wnt/β-catenin signaling pathway,inhibit the proliferation of intestinal epithelial cells,promote their apoptosis,destroy the intestinal barrier function,and induce intestinal structural injury.

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