美沙拉嗪干预溃疡性结肠炎相关癌变小鼠实验探究摘要:目的:观察美沙拉嗪防治渍疡性结肠炎相关癌变小鼠的实验研究。方法:60只清洁级Balb/c小鼠随机分5组,每组12只,正常组、模型组、低、中、高剂量治疗组;除外正常组,其余各组采用麗H/DSS复合法制备溃结癌变模型,模型组予等剂量生理盐水、治疗组分别予不同剂量美沙拉嗪干预9周。第9周末将全部小鼠脱椎处死,截取全部结肠(回盲部-肛门),肉眼及光镜下观察小鼠结肠组织形态学变化。结果:模型组小鼠结肠肉眼可见浆膜层散在、多处息肉状隆起变化,镜下见腺体萎缩、高级别上皮内瘤变,部分癌变;低剂量组肉眼见结肠黏膜充血水肿,部分可见溃疡样改变,镜下见黏膜充血肿胀,部分腺体萎缩;中、高剂量组肉眼见结肠黏膜充血、水肿,糜烂,镜下见黏膜上皮脱落,充血肿胀,未见溃疡及癌变,与模型组比较,有统计学意义(P<0.05)。各剂量组之间比较,无统计学意义(P〉0.05)。结论:美沙拉嗪具有防治溃结相关癌变的生物学效应。关键词:溃疡性结肠炎相关癌变;美沙拉嗪;实验研究分类号:R285.5文献标识码:A文章编号:1673-7717(2012)0卜0029-03TheinterventioneffectofMesalazineonpreventingulcerativecolitisassociatedcarcinogenesisYINHan今huanl,ZHANGTao2,LIJie^zhuang3,WENDa分xiong4(1.HeyuanPeople^sHospital,Heyuan517000,Guangdong,China;2.TheRuiKanghospitalaffiliatedGuangxiUniversityofTCM,Nanning530011,Guangxi,China)Abstract:Objective:ThemechanismofMesalazinepreventingulcerativecolitisassociatedcarcinogenesis(UCAC)wasdiscussedbyobservingthechangesof3-cateninandC~mycincolonmucosa.Methods:SixtyBalb/cratswererandomlydividedintofivegroups:Normalgroup,Blankgroup,Interventiongroup(lowdosage,milddosage,highdosage).Eachgrouphas12rats.Exceptnormalgroup,theothergroupswereintraperitonealinjectedwith0.4%DMH20mg/kgfortwotimesaweek.AfterintraperitonealinjectionofDMH,thosegroupsweregivenorally3%DSSfortwoweeks.Theaboveprocesswasrepeatedthreetimes.Theblankgroupwastreatedwithnormalsalinebyintragastricadministrationfortwentyweeks.ThoseinterventiongroupsweretreatedwithdifferentdosageofMesalazinebyintragastricadministrationfortwentyweeks.Thecolonhistomorphologywasassayedbynakedeyesandlightmicroscope.Result:Therearechangesofhyperemiaandedemaandpolypsoccupationincolonmucosaofblankgroupbynakedeyes.Meanwhile,thechangesofhigh-gradeintraepithelialneoplasiaandcarcinogenesiswereseeninblankgroup.Comparedwithinterventiongroup,thedifferenceisobvious(P<0.05).However,thehistomorphologychangesinlowdosageinterventiongroupischaracterizedbyhyperaemiaandulcerandlow-gradeintraepithelialneoplasia.Thehistomorphologymanifestiationinmild-highdosagegroupsarecharacterizedbyhyperaemiaandedema.Thereisnosignificantdifferenceinhistomorphologymanifestiationininterventiongroups(P>0.05).Conclusion:Mesalazinemayexertadistincteffectonpreventingulcerativecolitisassociatedwithcarcinogenesis.Keywords:ulcerativecolitisassociatedwithcarcinogenesis;Mesalazine;Experimentalstudy溃疡性结肠炎相关癌变(ulcerativecolitisassociatedcarcinogenesis,UCAC)是涉及多基因、多信号的复杂过程,2008-2010年在《nature》、《carcinogenesis》、《cell》等知名刊物发表文章相继指出,约80%的结肠癌与炎症密切相关,炎症作为第7大致癌因素而独立存在,控制炎症的发生、发展对于肿瘤的防治无疑是有利的[1-2]。现阶段,关于一线治疗溃结药物5-氨基水杨酸制剂预防溃结相关癌变报道较少;因此,课题组基于流行病学研究发现使用美沙拉嗪可明显降低溃结相关癌变的危险性[3],应用麗H/DSS制备溃结相关癌变模型,观察美沙拉嗪防治溃结相关癌变的研究。1材料1.1实验动物4周龄SPF级$BALB/c小鼠60只,许可证号:SCXK(粵)2008-0002,动物合...