溴隐亭治疗垂体腺瘤后超微结构改变和相关基因表达的研究  

Medical management of pituitary adenomas： a study of ultrastructural changes and receptor expressions

作　　者：吴哲褒[1] 张亚卓[2] 孙异临[2] 陈勇[1] 王成德[1] 苏志鹏[1] 吕庆平[1] 吴近森[1] 郑伟明[1] 诸葛启钏[1] 

机构地区：[1]温州医学院附属第一医院神经外科,325000 [2]北京市神经外科研究所

出　　处：《中华神经外科杂志》2011年第1期14-17,共4页Chinese Journal of Neurosurgery

基　　金：国家自然科学基金资助项目（30800347）;浙江省科技计划项目（2007C33028）;浙江省自然科学基金杰出青年团队项目（R2091137）

摘　　要：目的 从多巴胺2型受体表达水平和服药后细胞超微结构改变来阐明垂体腺瘤溴隐亭治疗的作用机制.方法 4例垂体无功能腺瘤和9例催乳素（PRL）腺瘤患者术前接受溴隐亭治疗,术后观察肿瘤细胞的超微结构改变.肿瘤标本送QRT-PCR检测细胞表面D2R和ER亚型的相对表达水平.结果 PRL腺瘤和临床无功能腺瘤细胞的D2S、D2L、ERα基因在mRNA水平存在差异表达（分别为P＜0.01,P＜0.01,P=0.019）,PRL腺瘤的表达水平明显较高.除1例颗粒密集型PRL腺瘤外,颗粒稀疏型PRL腺瘤服用溴隐亭后肿瘤细胞体积缩小,染色质异常凝集,胞质空泡变性,细胞器减少,可见裸核细胞、暗细胞和不同程度的细胞坏死崩解.垂体无功能腺瘤与PRL腺瘤比较,细胞大小、形态改变较少,胞质内细胞器未见明显减少,少见染色质边聚、胞质空泡变性和裸核细胞.结论 垂体无功能腺瘤和PRL腺瘤在D2R和ER受体水平存在差异表达.垂体无功能腺瘤中D2R表达水平高者也存在溴隐亭治疗后细胞的超微结构改变.溴隐亭治疗后垂体肿瘤细胞超微结构改变和D2R表达水平存在一定的相关性.Objective The aim of this study is to analyze the ultrastructural changes and dopamine 2 receptor（D2R） expression levels of pituitary adenomas to clarify the mechanism of medical management.Method 9patients with prolactinomas and 4 with nonfunctioning pituitary adenomas（ NFPAs）were treated with bromocriptine preoperatively.Ultrastructure changes of tumor cells were observed through electron microscopy.Tumor tissue samples were examined for the expression of both ER mRNA and D2R mRNA isoforms by means of QRT- PCR analysis.Results Expressions of D2S mRNA、 D2L mRNA、 ERα mRNA were significant difference between prolactinomas and NFPAs（ P ＜0.01, P ＜0.01, P =0.019,respectively）,in which was higher in prolac tinomas as compared to NFPAs.Except for 1 patient with densely granulated lact otroph adenomas,8 sparsely granulated lactotroph adenomas showed that cytoplasm was shrunken and the karyoplasmic ratio was enlarged.Ultrastructural analysis confirmed a series of changes including nuclear chromatin aggregation and margination,marked reduction of rough endoplasmic reticulum and Golgi complexes, vascular degenerations, necrosis and autolysis of tumor cells with dark cell or naked nuclear cell Compared to prolactinomas,NFPAs had little changes in cell size and cytoplasmic apparatus but also had chromatin aggregation, cytoplasmic vacuolization and unconspicuous necrosis of tumor cell.Conclusions This study shows the differential expression of ER mRNA and D2R mRNA isoforms between prolactinomas and NFPAs.Comparinb to prolactinomas,NFPAs with medical treatment also have some ultrastructural changes according to their exression levels of D2R isoforms.Ultrastructural changes in those adenomas are closely correlated with the expression levels of D2R isoforms.

关 键 词：催乳素腺瘤 垂体无功能腺瘤 溴隐亭 多巴胺2型受体 雌激素受体 超微结构 

分 类 号：R736.4[医药卫生—肿瘤]