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目的研究P it-1在垂体催乳素腺瘤发生中的作用。方法动物实验:⑴制备雌激素诱发的大鼠催乳素(PRL)瘤模型。成年雌性W istar大鼠切除卵巢后随机分两组,催乳素瘤组:皮下植入含有乙稀雌酚的硅胶管;对照组:皮下植入空白硅胶管;8周后处死动物,用放免法测定大鼠血清PRL水平,垂体称重并做组织病理学观察,用免疫组化方法显示垂体组织PRL蛋白的表达和分布。⑵用RT-PCR方法检测rP it-1 mRNA在两组垂体组织中的表达,以β-actin作为内参照,借助于计算机凝胶成像系统分析表达量。临床研究:⑴收集了31例垂体腺瘤标本,于液氮中保存。⑵用化学发光法测定患者术前外周血激素水平。⑶用RT-PCR方法检测hP it-1 mRNA在各组垂体腺瘤组织中的表达量。结果动物实验:用药8周后,根据大鼠血清PRL水平、垂体重量以及垂体组织学的改变,证实已诱发出催乳素瘤。rP it-1 mRNA在催乳素瘤组的表达水平明显高于对照组(P<0.001)。临床研究:31例垂体腺瘤患者,PRL瘤11例,生长激素(GH)瘤5例,PRL和GH混合瘤4例,无功能瘤11例,hP it-1 mRNA在所有PRL瘤、GH+PRL瘤、GH瘤和81.8%(9/11)无功能腺瘤中有表达。hP it-1 mRNA在PRL、GH和GH+PRL三组腺瘤中的表达量无明显差别,均明显高于无功能瘤组(P<0.01)。PRL瘤患者术前血清PRL值与腺瘤组织hP it-1表达量呈明显的正相关(r=0.90,P<0.01),GH腺瘤患者术前血清GH值与腺瘤组织hP it-1表达量呈明显的正相关(r=0.96,P<0.01)。结论⑴P it-1与垂体PRL基因的表达密切相关,在雌激素诱发的大鼠PRL瘤的形成中起一定的作用。⑵P it-1 mRNA在垂体腺瘤的细胞特异性表达形式,提示P it-1对垂体PRL腺瘤的特异性分化和其分泌功能起一定的作用。
Objective To study the role of P-1 in the development of pituitary prolactinomas. Methods Animal experiments: ⑴ Preparation of estrogen-induced rat prolactin (PRL) tumor model. Adult female W istar rats were ovariectomized randomly divided into two groups, prolactinoma group: subcutaneous implantation of silicone tube containing diethylstilbestrol; control group: a blank silicone tube implanted subcutaneously; 8 weeks after the animals were sacrificed by radioimmunoassay Serum PRL levels were measured, the pituitary gland was weighed and histopathologically observed. The expression and distribution of PRL protein in pituitary tissue were detected by immunohistochemistry. (2) RT-PCR was used to detect the expression of rPit-1 mRNA in the two groups of pituitary tissues. Β-actin was used as internal reference, and the expression of rPit-1 mRNA was analyzed by computer gel imaging system. Clinical study: ⑴ collected 31 cases of pituitary adenoma specimens, stored in liquid nitrogen. ⑵ chemiluminescence method for determination of preoperative peripheral blood hormone levels. (3) The expression of hP-1 mRNA in each group of pituitary adenomas was detected by RT-PCR. Results Animal experiments: After 8 weeks of treatment, prolactinomas were confirmed according to changes in rat serum PRL levels, pituitary weights and pituitary histology. The expression of rP-1 mRNA in the prolactinoma group was significantly higher than that in the control group (P <0.001). Clinical study: Among 31 patients with pituitary adenoma, 11 were PRL tumors, 5 were growth hormone (GH) tumors, 4 were PRL and GH mixed tumors, and 11 were nonfunctional tumors. The expression of hP-1 mRNA in all PRL tumors, GH + PRL tumors, GH tumors, and 81.8% (9/11) of non-functioning adenomas. The expression of hP-1 mRNA in PRL, GH and GH + PRL groups was significantly higher than that in non-functional tumor group (P <0.01). The PRL value of preoperative PRL tumor was positively correlated with the expression of hP-1 in adenoma (r = 0.90, P <0.01). The preoperative serum GH value and the expression of hPit-1 The expression level was positively correlated (r = 0.96, P <0.01). Conclusion (1) P it-1 is closely related to the expression of pituitary PRL gene and plays a role in the formation of estrogen-induced rat PRL tumor. Pit-1 mRNA in pituitary adenoma cell-specific expression, suggesting that P it-1 pituitary adenoma of PRL specific differentiation and secretion of a certain role.