胃粘膜上皮异型增生细胞增殖活性及凋亡与幽门螺杆菌感染的关系

背景与目的:异型增生是胃癌的癌前病变,但其癌变机制目前仍不清楚,本文通过对异型增生自然转归过程中细胞增殖活性和凋亡变化及幽门螺杆菌(Helicobacterpylori,HP)感染状态的研究,探讨二者之间的关系及其对异型增生癌变的影响。方法:取12例正常胃粘膜(对照组)和105例有随访结果的胃粘膜异型增生胃镜活检标本〔其中高度异型增生35例(癌变30例、未癌变5例);低度异型增生70例(癌变18例、未癌变52例)〕。全部标本均采用TUNEL(terminaldeoxynucleotidyltransferasemediatednickendlabeling)法检测凋亡情况;采用免疫组化法检测增殖细胞核抗原(proliferatingcellnuclearantigen,PCNA)表达情况;采用多聚酶链反应(polymerasechainreaction,PCR)检测HP及其CagA(+)株感染状况。结果:异型增生的HP感染率为84.76%,与对照组的83.33%相比差异无统计学意义,但CagA(+)株感染率为85.39%,高于对照组的60.00%。HP(+)和CagA(+)病例的增殖指数分别较HP(-)和CagA(-)为高(P<0.05),异型增生中PCNA的异常与HP及CagA(+)株感染有关(P<0.05)。凋亡/增殖比的变化与Hp的CagA(+)株感染有关(P<0.05)。结论:胃粘膜异型增生的形成及其自然转归过程中,异型增生的细胞动力学异常与HP、CagA(+)株感染有关。

Relationship between Helicobacter pylori infection and proliferation and apoptosis of gastric epithelial dysplasia cell

BACKGROUND & OBJECTIVE: Gastric epithelial dysplasia is the precancerous lesion of gastric cancer. However, the mechanism that dysplasia evolves to malignancy is not clear. In order to clarify the relationship between Helicobacter pylori (HP) infection and its virulence factor and changes of cell kinetics of dysplasia, the authors measured the changes of proliferation and apoptosis and the status of HP infection. METHODS: A total of 117 gastric mucosal biopsy specimens were enrolled, including 12 of chronic superficial gastritis (CSG) and 105 of dysplasia. Dysplasia samples were divided into two groups: 35 of high-grade dysplasia carcinogenesis group (n=30), regression group (n=5)], 70 of low-grade dysplasia carcinogenesis group (n=18), regression group (n=52)]. The expression of proliferating cell nuclear antigen (PCNA) was measured by immunohistochemical staining; cell apoptosis was determined by terminal deoxynucleotidyl transferase mediated nick end labeling(TUNEL); the status of HP infection was detected by polymerase chain reaction(PCR) with specific primers of urea A and cagA gene. RESULTS: There was no significant difference of HP infection between dysplasia and CSG(84.76% vs. 83.33%), but CagA-positive strain infection rate in dysplasia was slightly higher than that in CSG (85.39% vs. 60.00%). Proliferation indexes(PI) in the patients with HP infection and CagA(+) strain infection were higher than that in the patients without HP infection and CagA(-)strain, respectively (P< 0.05). PI was positively associated with the status of HP and CagA(+) strains infection (P< 0.05). AI/PI ratio (AI: apoptosis index) was negatively associated with CagA-positive strain infection (P< 0.05). CONCLUSION: Gastric epithelial dysplasia cells have abnormal changes in PI and AI when it evolves to malignancy, and the abnormal cell kinetics is partly correlated with HP and CagA(+) strain infection. So treatment of HP infection may produce a good result for the evolution of dysplasia.