南京军区南京总医院：垂体泌乳素腺瘤研究获进展

南京军区南京总医院神经外科医学博士李杰副教授在导师史继新教授指导下最新完成的“α-干扰素（IFN—α）和溴隐亭（BC）对垂体泌乳素（PRL）腺瘤细胞的作用”研究证实，IFN-α对体外培养的大多数PRL腺瘤，尤其是侵袭性垂体腺瘤细胞激素分泌有明显抑制作用，延长干预时间，其抑制作用更明显：同时对大多数对BC不敏感的垂体PRL腺瘤细胞激素分泌亦有抑制作用。     

浅谈垂体腺瘤手术病人的护理

垂体腺瘤是发生于腺垂体的良性肿瘤，约占肿瘤的10%-20％。主要有激素分泌活性腺瘤（功能型）：包括生长激素（GH）腺瘤，催乳素（PRL）腺瘤，促肾上腺皮质激素（ACTH）腺瘤，Nelson综合征，促甲状腺索（TSH）腺瘤，促性腺激素（FSH和LH）腺瘤。以入非激素活性的无功能细胞腺瘤。     

Pit-1基因在垂体催乳素腺瘤发生中作用的研究

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。     

甲状腺功能减退症与垂体发育相关性分析

目的探讨甲状腺功能减退症(甲减)与垂体发育的相关性。方法选取2009年12月—2015年12月收治的多种垂体激素缺乏症患者(multiple pituitary hormone deficiency,MPDH)44例,其中继发性甲减24例为继发性甲减组,非继发性甲减20例为非继发性甲减组;选取同期收治的甲减患儿40例为对照组,按照否合并有垂体增生分为垂体增生组30例和无垂体增生组10例;比较各组甲状腺激素水平(FT3、FT4、TSH)、生长激素(GH)、皮质醇(COR)、泌乳素(PRL)、垂体分泌卵泡刺激素(FSH),采用SPSS18.0进行统计学分析。结果继发性甲减组FT3、FT4、GH峰值、COR低于非继发性甲减组,PRL高于非继发性甲减组,差异均有统计学意义(均P0.05);其中FT4与GH峰值、COR、FSH呈正相关,与呈PRL负相关(均P0.05);垂体增生组TSH、PRL高于无垂体增生组,FT3、FT4低于无垂体增生组,差异均有统计学意义(均P0.05)。血清FSH与FT3水平呈负相关(均P0.05)。结论甲减与垂体发育不良、增生有一定的关系,一旦发现需要及时治疗,以免引起严重后果。     

内分泌紊乱，男人不例外

无论男人，还是女人，分泌乳汁都是在一种由脑垂体分泌的内分泌激素刺激下发生的，这种激素叫做“泌乳素”。一般情况下，妇女在怀孕后期及哺乳期泌乳素会大量分泌，以促进乳腺发育和乳汁分泌。泌乳素或催乳素，直观理解是女人在生育后哺乳阶段体内大量分泌的一种激素，可以促进乳汁的分泌。而在平时的状态下，泌乳素的水平是比较低下的，如果过高就可以给人体带来一些不必要的麻烦。泌乳素是脑下垂体分泌的，脑下垂体功能亢进，或者生长了小瘤子（垂体腺瘤），     

伽马刀结合手术切除与单独伽马刀治疗垂体腺瘤的疗效比较分析

目的 探讨伽马刀结合手术切除与单独伽马刀治疗垂体腺瘤的临床疗效,为其治疗提供依据.方法 共纳入175例诊断为垂体腺瘤患者,采用随机数字法分为两组,A组患者85例给予伽马刀结合手术切除治疗措施,B组患者90例给予单独伽马刀治疗,观察两组患者的疗效.结果 175例患者有160例(91.4％)症状得到缓解,其中伽马刀结合手术切除组79例(92.9％),单独伽马刀组81例(90.0％),两组比较差异无统计学意义(P＞0.05);治疗后与B组(单独伽马刀组)52例催乳素(prolactin,PRL)腺瘤患者及38例生长激素(Growth hormone,GH)腺瘤患者相比,伽马刀结合手术切除组48例PRL腺瘤患者血清PRL水平及37例GH腺瘤患者血清GH水平降低更明显,差异有统计学意义(P＜0.05);不同治疗方法头颅MRI检查及并发症比较结果显示,A组患者瘤体均缩小,B组有2例患者出现瘤体略变大,但症状未加重;两组患者均未有明显不良并发症的发生.结论 伽马刀结合手术切除垂体腺瘤的总体疗效好于单独伽马刀治疗患者,不仅可以改善患者的临床症状,且可以更明显降低患者的相关生化指标,值得临床推广应用.     

成年猪肺动脉内皮细胞的体外培养

目的：建立成年猪肺动脉内皮细胞（PAEC）的体外培养方法，为研究PAEC的功能提供新的实验模型。方法：采用游离血管外翻消化的方法进行体外培养，并对其进行鉴定和分泌功能的观察。结果；形态学和免疫学等鉴定方法证实，实验中培养中细胞为PAEC，同时具有良好分泌内皮素的生理功能。结论：建立的成年猪PAEC的体外培养方法，可做为研究PAEC在各种病理变化中作用机制的实验模型。     

细胞外基质及其与睾丸支持细胞的关系

细胞外基质对细胞结构和功能的调节作用在近年来受到重视。支持细胞在体外当生长在细胞外基质上时,形态和功能均更接近于在体的自然状态。特别是小鼠EHS瘤来源的重组基膜,可使支持细胞在体外形成高度极性化的上皮结构。另外,支持细胞也可合成和分泌部分细胞外基质成分。用重组基膜建立的双室培养模型,使得体外研究支持细胞的极性转运和双向分泌功能成为可能。     

催乳激素在培养猪颗粒细胞中对促卵泡成熟激素受体结合和孕酮产生的作用

近年来,催乳激素(PRL)被认为是一种生长调节剂,它可促进细胞的分化和增殖。一些研究显示,PRL在卵巢水平对修饰颗粒细胞功能有直接作用。体外研究表明,PRL可直接作用于颗粒细胞促进和抑制类固醇的生物合成以及黄体生成素受体的获得。本研究目的是进一步探讨在颗粒细胞水平PRL对促卵泡成熟激素受体(FSH-R)结合和孕酮(P)产生的作用。 本研究采用猪卵巢中的未成熟颗粒细胞,以多孔培养板进行培养,每孔8×10~6个细胞,常规培养4 d,培养基中均提供纯化的猪的FSH(10 ng/ml),但分别采用不加PRL     

HCV感染实验探讨人胎盘滋养层细胞分子生物性及侵袭力

目的探讨持续感染丙型肝炎病毒(HCV)对体外培养人胎盘合体滋养层细胞分子生物学性状及其金属蛋白酶(MMP)-2、MMP-9合成及分泌的影响。方法分别采用Matrigel人工重建基底膜侵袭实验、MTT法细胞黏附实验、细胞移动实验,研究HCV RNA阳性患者血清感染的体外培养人胎盘滋养层细胞(感染组)侵袭能力以及侵袭相关的黏附、移动能力的改变;检测培养上清中人绒毛膜促性腺激素(HCG)浓度以评估感染对细胞激素合成、分泌能力的影响。用酶联免疫吸附试验(ELISA)检测细胞培养上清MMP-2和MMP-9水平,分析感染组和对照组(健康体检者血清培养)数据间的差异,并用明胶酶谱进一步验证ELISA结果。应用逆转录聚合酶链反应(RT-PCR)法分析感染对细胞proMMP-2和proMMP-9 mRNA表达的影响。结果感染组细胞侵袭、黏附、移动以及激素合成、分泌能力较对照组细胞均显著下降(P0.05)。感染组细胞分泌MMP-2和MMP-9能力明显下降(与对照组比较,MMP-2:t=4.186,P0.05;MMP-9:t=2.325,P0.05);RT-PCR结果显示感染组细胞proM-MP-2和proMMP-9 mRNA表达弱于对照组,但差异无显著性(proMMP-2:t=1.196,P0.05;proMMP-9:t=1.417,P0.05)。结论持续HCV感染的体外培养人胎盘合体滋养层细胞MMP-2和MMP-9合成、分泌能力下降。持续感染HCV可抑制体外培养人胎盘合体滋养层细胞包括侵袭能力和激素合成、分泌能力在内的多种生物学功能。     

Prolactin in the immunological system: synthesis and biological effects

Prolactin (PRL) is a 23 kDa protein hormone that is produced and secreted by the pituitary lactotrophs. Although PRL was initially regarded as an exclusive pituitary hormone, many nonpituitary tissues were later found to contain and produce this hormone. The most established extrapituitary sites that produce PRL are the decidua, the immune system, brain and endometrium. In the immune system, PRL acts as a cytokine where it plays an important role in human immune responses, including in autoimmune diseases. Here, we will discuss the regulation of PRL gene expression in human lymphocytes and review the functions of PRL made by the immune cells, including its involvement in autoimmunity.     

人早孕流产蜕膜细胞的原代培养研究

目的建立纯度较高的适于实验研究的人蜕膜细胞。方法胶原酶I消化法培养人蜕膜细胞,光镜、扫描电镜、透射电镜观察细胞内部结构,间接免疫染色进行细胞鉴定。结果倒置显微镜下,可见细胞呈不规则多角形,呈片状铺展生长,核大卵圆形,胞质透明、糖原丰富,内质网扩张明显。免疫组化法检测细胞功能性指标胎盘催乳素,有99%培养的蜕膜细胞呈阳性。结论该法简便易行,可获得合乎实验要求的人蜕膜细胞,为进一步开展实验研究建立细胞模型。     

The presence of macromolecular prolactin in serum of pregnant women and patients with pituitary adenoma

The heterogeneity of immunoreactive Prolactin (IR-PRL) in serum of pregnant women and patients with pituitary adenoma were studied by Sephadex G-100 gel chromatography. The major IR-PRL peaks in serum of pregnant women were eluted at the position corresponding to that of 125I-PRL and the small amount of IR-PRL peaks were eluted near the void volume (peak 1) and between the void volume and 125I-PRL (peak 2). On the other hand, the proportion of peak 1 and peak 2 to total immunoreactivity was significantly increased in serum of patients with pituitary adenoma compared to those in serum of pregnant women. The rechromatographic studies under conditions of protein denaturation and sulfide cleavage on Sepharose CL-6B column revealed that the peak 1 of the pregnant women and patients with pituitary adenoma were eluted at the position between 125I-AFP and ovalbumine and the molecular weight was estimated to be about 54,000. This macromolecular PRL was also bound specifically to Sepharose coupled with anti-PRL, indicating that this macromolecule contained a sequence of PRL in its structure.     

Embryo implantation and embryonic stem cell development in primates

The endocrine dialogue that results in implantation and the successful establishment of pregnancy in primates relies on embryonic secretion of chorionic gonadotrophin (CG). This hormone is a signal of embryo viability and capacity to support the corpus luteum. The expression of CG is apparently restricted to primates. Active or passive immunization of marmoset monkeys against the beta subunit of CG prevented implantation and early pregnancy, without disrupting the ovarian cycle. Studies of individual embryos cultured in vitro showed that CG is secreted at low levels by the blastocyst from before attachment, with secretion increasing exponentially after attachment. Gonadotrophin releasing hormone (GnRH) was also secreted, from mid-blastocyst stages, before the detection of CG. The secretion of GnRH by the embryo continued through the attachment and outgrowth stages of embryonic differentiation in vitro. The hypothetical role of GnRH in regulating CG release during implantation was tested in recently completed experiments. Individual embryos cultured with GnRH, or with agonist or antagonist to GnRH, showed significant variations in their secretion of CG and in their survival in culture, suggesting a causal relationship between these hormones. Embryos cultured with natural GnRH showed enhanced growth and development. Embryonic stem cells, from the inner cell mass of marmoset and rhesus monkeys, were the first primate embryonic stem cells to be isolated and characterized, enabling the subsequent isolation of human embryonic stem cells.     

Effects of zinc deficiency upon pituitary function in sexually mature and immature male rats.

Serum pituitary levels of growth hormone (GH), thyrotropin (TSH), prolactin (PRL), luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured in sexually mature (adult) and sexually immature (juvenile) male rats who had been deprived of dietary zinc for 15 and 7 weeks, respectively. When compared to pair-fed control rats receiving a zinc supplemented diet, both the adult and juvenile zinc deficient rats had significantly lower body weights, tail lengths and ventral prostate weights. The testes of the sexually immature rats were also smaller than those of the pair-fed animals. In sexually mature, zinc deficient rats serum concentrations of GH and testosterone were significantly lower and serum LH levels significantly higher than in ad libitum fed control rats. Pituitary and hypothalamic levels of other hormones did not differ from values recorded in control animals. In sexually immature zinc deficient rats serum concentrations of GH were also significantly depressed; pituitary content and concentration of LH and pituitary and serum levels of FSH were significantly increased over control values. No discernible effects of zinc deficiency upon hyplthalamic content of LH-releasing hormone or serum concentrations of PRL or TSH were recorded in juvenile rats. Zinc deficiency has minimal effects upon the hypothalamic-pituitary axis of sexually mature rats. In sexually immature males, zinc deprivation leads to impairment of gonadal growth and increased synthesis and/or secretion of the pituitary gonadotropins.     

Pitutaty insufficiency. Diagnosis masked by a toxic thyroid adenoma

A patient with undiagnosed pituitary insufficiency who also had a toxic thyroid adenoma is presented. The T3 secreted by the adenoma apparently corrected the secondary thyroid failure, but also aggravated the secondary adrenal failure and almost precipitated adrenal crisis. The diagnostic work-up in such an unusual co-existence is discussed, in particular since the clinical diagnosis of pituitary insufficiency in the elderly is not easily established.     

42例垂体腺瘤的视野分析

目的分析垂体腺瘤患者双眼的眼部临床表现及中心视野的改变。方法应用Humphrey Ⅱ-750型电脑视野分析仪,对42例垂体腺瘤患者行全阈值静态中心视野检查。结果眼底原发性视神经萎缩32眼,占38．1％;54眼有视野缺损,占64．3％,其中24眼出现典型的双颞侧偏盲;33例（66眼）患者接受手术治疗,术后6个月复查视野,53眼明显好转,占80．3％。结论垂体腺瘤可引起视功能的损害,充分认识垂体腺瘤在眼部的临床表现,有助于早期诊断和治疗,避免漏诊、误诊。     

内分泌激素水平与垂体瘤手术远期疗效相关性分析

[目的]通过临床对垂体瘤手术患者给予内分泌激素水平检测,分析其与患者远期治疗效果的相关性以及观察意义。[方法]选取某院2008年1月～2010年1月所收治的垂体瘤临床经显微外科手术治疗的患者274例进行回顾性分析,动态观察患者手术前后血清泌乳素、甲状腺功能(促肾上腺皮质激素和血皮质醇)以及生长激素的水平变化,并对所有患者给予1年的随访观察,分析其远期治疗效果。[结果]274例垂体瘤手术患者在术后1周内血清泌乳素、生长激素水平相较于手术前明显下降,并且术后随访观察一直维持。274例患者中有68例垂体生长激素腺瘤患者,患者在术后有22例患者生长激素下降到0.34nmol/L,46例患者生长激素下降程度未达到0.34nmol/L以下,术后随访观察有26例患者有病情复发的表现。[结论]患者在手术后以生长激素下降到0.34nmol/L以下为治愈,而内分泌激素水平的检测能够有效判断垂体瘤患者术后的治疗效果,在临床具有非常高的诊断意义与价值。     

MIS,IGF-Ⅱ对人卵巢黄素化颗粒细胞分泌功能的影响

目的:探讨MIS,IGF-Ⅱ对人卵巢黄素化颗粒细胞分泌雌激素的影响。方法:体外受精-胚胎移植(IVF-ET)患者经阴道超声引导下取卵,剥离卵母细胞周围的颗粒细胞作体外培养,培养48h后更换无血清培养基,在有或无卵泡刺激激素(FSR)的作用下,分别加入基因重组人苗勒氏管抑制因子(rhMIS)及人胰岛素样生长因子Ⅱ(rhIGF-Ⅱ)作用于颗粒细胞,于培养后第4、6、8、10天收集培养液测定雌二醇(E2),观察rhMIS及rhIGF-Ⅱ对体外培养的颗粒细胞分泌E2的影响。结果:在无FSH作用下,rhMIS对颗粒细胞分泌E2无明显影响(P>0·05),rhIGF-Ⅱ刺激颗粒细胞分泌E2量增加(P<0·05);加入FSH后,rhMIS的明显抑制颗粒细胞E2分泌量(P<0·05),rhIGF-Ⅱ明显增加颗粒细胞E2的分泌(P<0·05)。结论:MIS和IGF-Ⅱ可单独或协同FSH刺激颗粒细胞甾体激素的分泌,对卵泡的生长发育及卵母细胞的分化成熟起着微观调控作用。     

Magnetization transfer imaging of the pituitary gland

Magnetization transfer (MT) techniques provide tissue contrast which depends mainly on the concentration of macromolecules. The magnetization transfer phenomenon is determined by the restricted macromolecular protons and is quantified by the magnetization transfer ratio (MTR). Since many macromolecular structures are implicated in the secretory activity of the pituitary gland, this imaging technique has recently been used for the study of the normal adenohypophysis and the pre-operative and post-operative evaluation of pituitary adenomas. Significant changes of the MTR with age occur in normal subjects. In patients with hyperprolactinemia, the MTR of prolactin-secreting tumors is higher and that of the non secreting adenomas is lower compared to the MTR values of the normal pituitary gland of age and sex matched controls. In some patients operated on for growth hormone adenomas, although classic MR images were negative for residual tumor, increased MTR values were highly suggestive of persistence of adenoma tissue, in agreement with biochemical findings of persisting secretory activity. These data suggest that MT techniques might be an additional useful tool in the assessment of pituitary gland disorders.