二甲双胍、塞来昔布对化学诱导小鼠结直肠异常隐窝病灶预防作用的比较  

Chemopreventive effects of metformin or celecoxib on chemically induced colorectal aberrant crypt foci in mice

作　　者：李达周[1] 王雯[2] 许斌斌[2] 王蓉[2] 刘建强[2] 林克荣[2] 邹多武[3] 

机构地区：[1]第二军医大学福州临床医学院南京军区福州总医院消化科,福建福州350025 [2]南京军区福州总医院消化科,福建福州350025 [3]第二军医大学附属长海医院消化科,上海200433

出　　处：《临床消化病杂志》2016年第3期133-136,共4页Chinese Journal of Clinical Gastroenterology

基　　金：福建省重点项目基金资助(No:2014Y0038)

摘　　要：[目的]探讨二甲双胍对氧化偶氮甲烷(AOM)诱导的小鼠结直肠异常隐窝病灶(ACF)的预防作用,并与塞来昔布进行比较。[方法]45只6周龄BALB/c雌性小鼠随机分为对照组、二甲双胍组、塞来昔布组,每组15只;均腹腔注射AOM(10mg/kg),每周1次,连续2周以建立ACF模型;同时对照组、二甲双胍组、塞来昔布组小鼠分别予0.9%氯化钠溶液0.5ml·只^(-1)·d^(-1)、二甲双胍250mg·kg^(-1)·d^(-1)、塞来昔布20mg·kg^(-1)·d^(-1)灌胃处理,每周监测小鼠体质量变化。6周后处死小鼠并分离结直肠组织,美蓝染色后计数每只小鼠结直肠ACF个数和每个ACF中畸变隐窝(AC)个数。[结果]各组小鼠体质量随周龄增加均呈现增长趋势,干预后体质量比较均差异无统计学意义(P>0.05)。对照组小鼠结直肠ACF及AC数量分别为(8.80±0.84)个、(26.75±2.63)个,二甲双胍组分别为(3.67±0.58)个、(8.33±0.58)个,塞来昔布组分别为(5.60±0.89)个、(13.40±1.67)个;与对照组相比,二甲双胍组、塞来昔布组小鼠ACF及AC均显著减少(P<0.05);二甲双胍组小鼠ACF及AC均比塞来昔布组显著减少(P<0.05)。[结论]二甲双胍、塞来昔布均能显著抑制ACF形成,对结直肠癌起到预防的作用,且二甲双胍的作用明显优于塞来昔布。[Objective]To investigate chemopreventive effects of metformin or celecoxib on chemically induced colorectal aberrant crypt loci in mice. [Methods]Forty-five 6-week-old BALB/c female mice were randomly divided into 3 groups.control group,metformin group and celecoxib group. After one week adap- tation,the mice were injected intraperitoneally with 10 mg/kg of AOM,once a week for two weeks. The mice in control group,metformin group and celecoxib group were treated with saline,metformin（250 mg ·kg^-1 · d^-1）and celecoxib（20 mg · kg^-1 · d^-1）by gavage,respectively. The changes of body weight were monitored weekly in mice. After 6 weeks,mice were sacrificed and the colorectal tissues were collected. The ACF and aberrant crypt（AC）in the colorectal mucosa were assessed after stained with methylene bule. 1-Re- suits]There was no significant difference between the average weight in the 3 groups of mice after the drug intervention（P）0.05）. The average numbers of colorectal ACF and AC in control group mice were 8.80± 0. 84,26. 75±2. 63 respectively. The average numbers of ACF and AC in metformin group were 3.67± 0.58,8.33 ± 0.58 respectively. The average numbers of ACF and AC in celecoxib group were 5.60± 0.89, 13.40±1.67 respectively. Comparing with the control group,the numbers of ACF and AC in the metform- in group and celecoxib group were significantly lower（P〈0.05）. There was significant difference between metformin group and celecoxib group（P〈0.05）. [Conclusion]We confirm the effect of metformin and cele- coxib on ACF suppression, which may play a preventive role for colorectal cancer（CRC）. Moreover, the effect of metformin is superior to celecoxib.

关 键 词：结直肠癌 异常隐窝病灶 二甲双胍 塞来昔布 化学预防 

分 类 号：R735.34[医药卫生—肿瘤]