细胞色素P450代谢途径相关基因在口腔黏膜下纤维化中的表达分析

Expression of cytochrome P450 related genes in oral submucous fibrosis tissue

目的探讨细胞色素13450（cytochrome13450，CYP）代谢途径相关基因在口腔黏膜下纤维化（oral submucous fibrosis，OSF）发病中的作用。方法收集就诊于长沙市口腔医院牙周黏膜科、中南大学湘雅二医院口腔医学中心的OSF颊黏膜组织（早、中、晚期OSF各lO例）及长沙市口腔医院口腔颌面外科手术中切除的10例健康颊黏膜组织（健康对照组），应用cDNA芯片技术建立OSF相关基因差异表达谱，提交数据库分析，筛选CYP代谢途径相关差异表达基因。应用反转录聚合酶链反应（reverse transcription-polymerase chain reaction，RT—PCR）进一步扩大样本量检测基因的表达改变。结果cDNA芯片检测得到与CYP代谢途径相关的CYP286、CYP2C18、CYV2F1、CYP3A5、微粒体谷胱甘肽s转移酶2、醇脱氢酶5、尿苷二磷酸葡萄糖醛酸转移酶2815、醇脱氢酶1C共8个基因在OSF组织中呈差异表达。经RT-PCR进一步扩大样本量检测证实，OSF早、中、晚期的组织中CYP代谢途径相关的8个基因mRNA均表达下调，与健康对照组的相应基因mRNA表达差异均有统计学意义（P〈0．001）；OSF早、中、晚期的基因表达差异均无统计学意义（P〉0．05）。结论OSF早、中、晚各期组织中存在异常下调表达的CYP代谢途径相关基因，提示CYP代谢途径对槟榔成分代谢清除能力下降，可能是OSF的发病机制之一。

Objective To examine the expression of cytochrome P450 related genes in oral submucous fibrosis tissue and to investigate the possible role of the genes in pathogenesis of oral submucous fibrosis（OSF） Methods Buccul mucosa tissues were obtained from OSF patients in early, medium and advanced stages, with each stage including 10 patients. Normal buccul mueosa tissues were collected from 10 patients undergoing oral and maxillofacial surgery as control. Oral submucous fibrosis-related genes were analysed by cDNA chips, and the results were submitted to the gene network database. Differentially expressed genes related to the pathway of CYP metabolism were indentifyed by the database analysis. Reverse transcription- polymerase chain reaction （RT-PCR） was used to verify the results from cDNA chips by increasing sample volume. Results There were eight genes [ CYP2B6, CYP2C18, CYP2F1, CYP3AS, microsomal glutatbione S-transferase 2 （ MGST2 ）, alcohol dehydrogenase （ADH）, UDP glucuronosyl transferase 2B15 （ UGT2B15 ）, ADH1C] which were related to the pathway of CYP metabolism. These genes were low expressed in all stages of OSF（P 〈0. 001 ）. There were no differences in genes expression among the three stages of OSF（P 〉0. 05）. Conclusions There were down-regulated genes related to the pathway of CYP metabolism in oral submucous fibrosis tissue. The ability of the pathway of CYP to metabolize and clear betel nut ingredients was reduced in OSF patients,which may play a role in the pathogenesis of OSF.