【作者】 陈富勇；

【导师】 王守森； 王如密；

【作者基本信息】 福建医科大学 ， 外科学， 2006， 硕士

【摘要】 垂体腺瘤发病率高,约占颅内肿瘤的15%。大部分垂体腺瘤能分泌激素,如催乳素、生长激素,在催乳素细胞腺瘤和/或生长激素细胞腺瘤中,多巴胺受体激动剂和/或生长抑素大部分能有效地抑制催乳素或生长激素的分泌,并且能明显的抑制肿瘤生长或使肿瘤缩小。然而,一部分催乳素细胞腺瘤和生长激素细胞腺瘤患者对于这些药物治疗不敏感或呈耐受状态。无功能性垂体腺瘤也有很高的发病率,目前尚没有有效的药物治疗手段。因此,随着垂体腺瘤分子发病机理研究的深入,寻找合适的药物作用靶点、开发新的安全而有效的治疗药物,对于提高垂体腺瘤,尤其是无功能垂体腺瘤、巨大垂体腺瘤以及侵袭性垂体腺瘤的整体治疗水平至关重要。目的:本文研究PPAR-γ高亲和力配体——噻唑烷二酮类药物中的曲格列酮,对大鼠垂体腺瘤GH3细胞系的抗瘤作用,并初步的探讨其作用机制。方法:以GH3细胞为研究对象,将实验对象分为空白对照组、DMSO对照组、10^-7M曲格列酮组、10^-6M曲格列酮组、10^-5M曲格列酮组。在药物干预后5d内,用MTT法连续检测各组GH3细胞的增殖抑制率;在药物干预前及干预后3d内,用放射免疫法连续测定各组GH3细胞的上清液的PRL量;在药物干预后72h,用流式细胞技术检测各组GH3细胞周期的变化,用免疫组化法检测各组PCNA蛋白表达,用RT-PCR方法检测各组Survivin、Cyclin D₁、Caspase3基因mRNA表达。结果: MTT实验显示,GH3细胞在曲格列酮干预下,随着药物作用时间的延长,药物浓度的增加,GH3细胞增殖抑制率进行性增加,尤其在药物作用后72h,各干预组与DMSO对照组的GH3增殖抑制率比较有显著的差更多还原

【Abstract】 Pituitary adenomas acount for approximately 15% of intracranial tumors. Some pituitary tumors secret hormone such as prolactin and growth hormone, and in most of these PRL- and GH-secreting pituitary adenomas, dopamine agonists and /or somatostatin analogues effectively suppress PRL and GH hypersecretion, respectively and control tumor growth or induce tumor shrinkage. Nevertheless ,a subset of patients with PRL- and GH-secreting pituitary adenomas do not respond to or are intolerant of these drugs. Non-functioning pituitary adenomas are general macroadenomas and cause significant morbidity and ultimately mortality. No effective drug therapies for nonfunctioning pituitary adenomas currently exist. Therefore, with the thorough development of research on molecular pathogenesis of pituitary adenomas. It’s essential to search suitable target of drug action and exploit novel, safe and effective drug for pituitary adenomas, which can enhance the curative effect of pituitary adenomas, especially nonfunctioning pituitary adenomas, macro-pituitary adenomas and invasive pituitary adenomas.ObjectiveTo study the antitumor effects of thiazolidinedione compounds—troglitazone, which is a strong affinity ligand of peroxisome proliferrator- activated receptor–γ, on rat pituitary adenomas GH3 cell line in culture and explore the mechanisms for this antitumor effects preliminarily.Methods更多还原