H.pylori对MGs胃黏膜Cx32、Cx43及相关转录因子表达的影响

Effects of H.pylori on the expression of Cx32,Cx43 and related transcription factors in Mongolian gerbils

目的观察幽门螺杆菌(Helicobacter pylori,H.pylori)对蒙古沙土鼠(Mongolian gerbils,MGs)胃黏膜Cx32、Cx43和转录因子GATA-3、AP-4、PBX-1、C/EBPβ表达的影响及其相关性,探讨H.pylori致癌的机制。方法实验组采用经胃镜及病理确诊的胃癌患者胃黏膜分离的H.pylori对36只MGs灌胃,对照组5只用灭菌PBS灌胃;分批处死,观察H.pylori灌胃后第4、24、48、72周MGs H.pylori定植和胃黏膜病变情况,及Cx32、Cx43和转录因子表达变化。结果实验组H.pylori定植率为80.0%,灌胃后第4、24周MGs胃黏膜肉眼见充血水肿或糜烂、出血,HE染色呈不同程度慢性非萎缩性胃炎(NAG),48周后6例肉眼见胃黏膜变薄、颜色灰暗,HE染色4例慢性萎缩性胃炎(CAG)、2例肠化(IM),对照组无H.pylori定植,胃黏膜肉眼及HE染色无明显异常;实验组较对照组MGs胃组织Cx32、Cx43表达显著下降,转录因子GATA-3、AP-4、PBX-1、C/EBPβ表达显著升高(P<0.05),其中有胃癌前病变(CAG和IM)者较NAG者改变明显(P<0.05);Cx32、Cx43与转录因子表达呈负相关(-1<r<0,P<0.05)。结论 H.pylori感染上调MGs胃黏膜转录因子GATA-3、AP-4、PBX-1和C/EBPβ表达,下调Cx32、Cx43表达,可能与胃癌发生有关。

Objective To observe the expression of Cx32,Cx43,GATA-3,AP-4,PBX-1and C/EBPβmRNA as well as their relationship in gastric mucosa of Mongolian gerbils（MGs）infected with H.pylori,and investigate the mechanism of H.pylori causing cancer.Methods 36 MGs were infected with H.pylori isolated from gastric mucosa pathologically diagnosed as gastric carcinoma;another 5MGs were inoculated with sterilized PBS and served as the controls.The animals were sacrificed at the 4th,24 th,48th and 72 th week respectively to observe the pathological changes,H.pylori colonization and expression of Cx32,Cx43 and transcription factors.Results The colonization rate of H.pylori in experimental group was 80.0%.At the 4th and 24 th week after H.pylori infection,hyperemia edema,erosion or bleeding,and different degrees of non-atrophic gastritis were observed.At the 48 th week,the mucosa of 6MGs turned thin;glandular atrophy and intestinal metaplasia were seen in 4and 2 MGs respectively.There was no H.pylori colonization in control group,and the gastric mucosa of the controls remained normal.Compared with control group,the expression of Cx32 and Cx43mRNA decreased magnificantly,while the expression of transcription factors GATA-3,AP-4,PBX-1and C/EBPβincreased magnificantly in exprimental group（P〈0.05）.The expression of transcription factors in MGs with precancerous lesions（CAG and IM）changed significantly compared with those in MGs with non-atrophic gastritis（P〈0.05）.The expression of Cx32 and Cx43was negatively correlated to transcription factors（-1r0,P〈0.05）.Conclusion H.pylori infection may up-regulate the expression of GATA-3,AP-4,PBX-1and C/EBPβwhile down-regulate the expression of Cx32 and Cx43,which might correlate to the gastric carcinogenesis.