间隙连接蛋白43在舌黏膜癌变过程中的表达

摘要

Objective To study the expression of connexin 43 (Cx43) in various stages of oral carcinogenesis and explore the relation between Cx43 and oral mucous carcinogenesis.Methods 4 nitroquinoline 1 oxide (4NQO) was used for inducing oral carcinogenesis in SD rats.Tissue samples were obtained from various stages of the disease including normal oral mucosa,precancerous lesions and oral squamous cell carcinoma.Immunohistochemical method was used to determine the expression of Cx43 in various stages of oral carcinogenesis.Results In the normal rat lingual mucosa,immunohistochemical staining of Cx43 protein was mainly found in the cell membrane,weakly positive in the basal cell layer,increased in stratum spinosum and stratum granulosum,but was negative in the stratum corneum of normal epithelia.Compared with normal epithelia,was significantly decreased in dysplastic and cancerous oral epithelia the staining.The positive rates of Cx43 were respectively 100.00％ (10/10),85.71％％ (12/14),66.67％ (8/12),40.00％ (4/10),and 33.33％ (4/12) in tongue carcinogenesis (in normal,mild,moderate and severe dysplasia,and squamous cell carcinoma tissues).The differences were statistically significant (P＜0.05).Conclusions Expression level of Cx43 protein was dramatically decreased with the development of rat tongue carcinoma induced by 4NQO,suggesting that abnormal expression of Cx43 protein is involved in oral mucosa carcinogenesis.Decreased Cx43 expression is an early sign of oral mucosa carcinogenesis.%目的 研究间隙连接蛋白43(connexin 43,Cx43)在口腔黏膜癌变过程中的表达变化,探寻其与口腔黏膜癌变的关系及意义.方法 用4亚基硝氧喹啉(4-nitroquinoline-1-oxide,4NQO)诱导SD大鼠口腔黏膜癌变,应用免疫组化方法检测Cx43在口腔黏膜癌变过程中各阶段的动态变化,分析Cx43与口腔黏膜癌变的关系.结果 Cx43蛋白主要表达于大鼠舌黏膜上皮细胞的胞膜、上皮基底层、棘层和颗粒层呈阳性染色,角质层未见表达.随着舌黏膜上皮异常增生程度的增加,Cx43的表达明显下降.在口腔鳞状细胞癌组织中,Cx43染色分布于癌细胞胞质以及鳞癌组织的角化珠内.Cx43在正常舌黏膜、轻度上皮异常增生、中度上皮异常增生、重度上皮异常增生、口腔鳞癌组织中阳性表达率分别为100.00％(10/10)、85.71％(12/14)、66.67％(8/12)、40.00％(4/10)、33.33％(4/12),差异有统计学意义(P＜0.05).结论 4NQO诱发舌黏膜癌变的过程中,Cx43蛋白表达水平随病变程度加重而显著下降,提示Cx43表达异常参与了口腔黏膜的癌变过程.Cx43表达下降是口腔黏膜癌变的早期事件.