人嗅粘膜内细胞色素P450 2A6的发育表达

Developmental expression of Cytochrome P450 2A6 in human olfactory mocosa

目的:探讨细胞色素P4502A6(cytochromeP4502A6,CYP2A6)在不同胎龄胎儿嗅粘膜内的发育表达。方法:应用免疫组化法观察CYP2A6在胚胎发育16、18、22、28和38周胎儿嗅粘膜内的表达情况。结果:CYP2A6的表达始于孕18周,在支持细胞核上区胞浆顶端阳性着色,彼此相连呈一条带状,上皮中、下层个别支持细胞核下区也呈现稍弱的免疫阳性反应。到孕22周时,固有层Bowman腺细胞浆内开始出现CYP2A6阳性着色,但此时Bowman腺体数量较少,腺细胞仅单层排列围成腺腔。随胎儿发育CYP2A6表达强度不断增大,孕28周时整个支持细胞的阳性着色更加清晰,固有层内Bowman腺数量明显增多,并且腺细胞呈多层排列,胞浆内CYP2A6阳性强度开始超出上皮层内的支持细胞。孕38周时免疫反应达峰值,其中支持细胞的染色勾画出其独特的极性结构:细胞核上区宽阔,胞浆内CYP2A6染色清晰,而核下区逐渐缩窄,以足状突的形式附着于基膜上。结论:人胎儿发育时期嗅粘膜内有CYP2A6酶表达,并且与嗅感受神经元发育基本同步,二者可能存在共同的调控因子。固有层Bowman腺细胞内CYP2A6的开始表达时间晚于上皮层支持细胞,但却是嗅粘膜内CYP2A6表达的主要部位以及嗅素代谢转化的主要场所。

Objective:To study the expression of cy tochrome P4502A6(CYP2A6)in the developing olfactory mucosa.Methods:T he expression of CYP2A6in the olfactory mucosa of human fetuses at weeks of1 6,18,22,28and38was observed by immunohistochemistry.Results:CYP2A 6immunoreactivity was first observed in the apical cytoplasm of sustentacular c ells(SCs)in the epithelium at gestational week18(W18),and the infranucl ear region of a few SCs located in the middle-lower portion of the epithelium showed weak immunoreactivity at this stage.The cytoplasm of acinar cells of Bow man glands(BGs)in the laminar propria became immunopositive from W22,altho ugh the numbers of BGs were limited and the lumens were only enclosed by single-layered cells at that time.With the progression of the development the inten sity of CYP2A6immunoreactivity increased.The immunoreactivity in the SCs was remarkable at W28,the number of BGs increased sharply and the lumens were e nclosed by multilayered acinar cells,the intensity of immunoreactivity in the a cinar cells of BGs exceeded that in SCs in the epithelium from that time on. The immunoreactivity reached its highest level at W38and the staining pattern of SCs represented its uniqu e structures:the apical re-gions with strong CYP2A6immunoreactivity were bro ad,while the infranuclear region began to narrow gradually into foot process wh ich was attached with the basement membrane.Conclusion:The expres-sion of CY P2A6in the olfactory mucosa began at fetal stage and was synchronous with the develop-ment of olfactory sensory neurons,indicated that they may have the sa me regulatory factors.The initial time of expression of CYP2A6in BGs was l ater than that in SCs,but BGs were the predominant site of CYP2A6expressio n and odorant metabolism in olfactory mucosa.