溴隐亭治疗高泌乳素血症的临床观察

目的:评价溴隐亭治疗高泌乳素(PRL)血症的临床疗效。方法:治疗组87例,其中单纯性高PRL血症24例,脑垂体PRL微腺瘤42例、大腺瘤21例。设健康对照组36例。治疗组均予口服溴隐亭,开始量每晚为1.25mg,隔3d增加1.25mg,直到2.5mg,tid;在治疗前及治疗后12周、24周分别测定血清PRL,同时做脑垂体磁共振。结果:治疗12周后与治疗前同性别组比较,PRL值明显下降(P<0.05),但仍高于同性别对照组(P<0.05);治疗24周后PRL值比治疗前同性别组显著下降(P<0.01),且与同性别对照组无显著性差异(P>0.05)。12周后,单纯性高PRL血症治愈率达100%,垂体PRL微腺瘤总有效率为42.86%;24周后,垂体PRL微腺瘤治愈率为14.29%,总有效率为80.95%,垂体PRL大腺瘤总有效率为42.86%。结论:溴隐亭治疗高PRL血症可使血PRL恢复正常,垂体PRL腺瘤缩小甚至消失。     

溴隐亭治疗泌乳素大腺瘤的临床观察

目的:探讨溴隐亭治疗泌乳素大腺瘤的方法、效果及不良反应。方法:回顾性分析单纯溴隐亭治疗9例泌乳素大腺瘤的长期随访结果。结果:溴隐亭的开始剂量为1.25～2.5 mg.d-1、分2～3次口服,在6个月内缓慢增至5～15 mg.d-1。平均随访58.3个月,最后随访时血泌乳素(prolactine,PRL)恢复正常8例(88.89%)、肿瘤体积平均缩小(81.3±23.9)%。治疗期间大部分原发症状好转,出现头晕2例、脑脊液漏1例。结论:溴隐亭单药治疗泌乳素大腺瘤能明显降低血PRL、缩小肿瘤体积及改善临床症状,且不良反应少。     

溴隐亭或伽玛刀治疗垂体泌乳素腺瘤30例

目的：探讨口服溴隐亭和伽玛刀治疗垂体泌乳素腺瘤的临床疗效。方法：对３０例垂体泌乳素腺瘤患者,经口服溴隐亭或伽玛刀治疗前后的临床症状、血清泌乳素（ＰＲＬ）水平、肿瘤体积等方面的改变进行了比较。结果：口服溴隐亭组,经皇其血甭ＰＲＬ水平降低优于伽玛刀组,两组有显著性差异（Ｐ〈０．０１）,肿瘤体积缩小则伽玛刀组优于省隐亭组（Ｐ〈０．０１）。结论：垂体沁乳腺瘤患者口服溴隐亭近期疗效显著,伽玛刀治疗后症着改善     

溴隐亭或伽玛刀治疗垂体泌乳素腺瘤30例

目的：探讨口服溴隐亭和伽玛刀治疗垂体泌乳素腺瘤的临床疗效。方法：对３０ 例垂体泌乳素腺瘤患者,经口服溴隐亭或伽玛刀治疗前后的临床症状、血清泌乳素（ Ｐ Ｒ Ｌ） 水平、肿瘤体积等方面的改变进行了比较。结果：口服溴隐亭组,经治疗后其血清 Ｐ Ｒ Ｌ 水平降低优于伽玛刀组,两者有显著性差异（ Ｐ＜ ００１） , 肿瘤体积缩小则伽玛刀组优于溴隐亭组（ Ｐ＜ ００１） 。结论：垂体泌乳素腺瘤患者口服溴隐亭近期疗效显著,伽玛刀治疗后症状改善不显著者加服溴隐亭仍有效,其远期疗效尚待进一步观察。     

单鼻孔经蝶手术切除泌乳素微腺瘤效果评价

目的分析单鼻孔经蝶手术切除泌乳素微腺瘤的效果及影响预后的相关因素。方法结合文献资料回顾性分析2001年8月至2004年1月我们收治的泌乳素微腺瘤患者临床资料并依据术前血泌乳素（PRL）水平将所有患者按PRL≤100μg／L、100μg／L-200μg／L及PRL〉200μg／L分为3组研究。结果21例患者术后12例PRL水平恢复正常。3组患者术后PRL恢复正常和闭经患者恢复正常月经周期的比率分别为100％（7／7）、80％（4／5）、11．1％（1／9）和66．7％（2／3）、66．7％（2／3）、14．3％（1／7）。7例月经紊乱患者中6例（85．7％）月经恢复正常，78．6％（11／14例）的患者溢乳消失。术前曾用溴隐亭的患者与未用溴隐亭的患者手术疗效比较差异无显著性。结论单鼻孔经蝶手术是治疗泌乳素微腺瘤的有效手段．术前血PRL水平是影响手术预后的主要因素，术前溴隐亭治疗对手术预后无显著影响。     

溴隐亭对泌乳素腺瘤术后治疗作用的临床研究

目的 探讨溴隐亭对泌乳素腺瘤术后的治疗效果.方法 回顾性分析非侵袭性泌乳素腺瘤15例、侵袭性泌乳素腺瘤6例患者的术后治疗效果.结果 术后口服溴隐亭在控制术后高泌乳素血症、随访中控制肿瘤复发方面均与未口服组比较存在显著性差异（P＜0.05）.结论 肿瘤的生物学性质影响治疗方式的选择和最终预后水平.对于手术切除肿瘤后部分患者仍存在内分泌紊乱的激素异常和临床症状,术后合理地口服溴隐亭能有效恢复垂体正常生理功能,缩小肿瘤和降低肿瘤复发,增强手术效果,提高患者生活质量.     

影响泌乳素型垂体腺瘤患者服药依从性的原因及对策

目的分析影响泌乳素型垂体腺瘤患者服药依从性的原因并提出相应对策,以提高服药依从性。方法调查分析97例口服溴隐亭治疗泌乳素型垂体腺瘤患者服药依从性下降的原因。结果97位患者服药依从性良好42例,下降55例。依从性下降的原因包括相关知识缺乏、错误21例（38．2％）、药物副作用15例（27．3％）、经济原因13例（23．6％）、溴隐亭抵抗6例（10．9％）。结论口服溴隐亭治疗泌乳素型垂体腺瘤患者服药依从性下降的原因较多：针对性的对策可提高患者服药依从性。     

经鼻蝶泌乳素型垂体腺瘤手术治疗的临床疗效分析

目的探讨经单侧鼻孔蝶窦入路手术切除泌乳素(PRL)型垂体腺瘤的疗效。方法回顾性分析2009年1月至今收治20例泌乳素腺瘤患者的临床及影像资料,根据术前血PRL水平分成3组进行手术疗效对比分析,分别为:<100ng/mL、100ng/mL～200ng/mL及>200ng/mL。结果本组患者无死亡病例,术中术后未见出血、无脑脊液鼻漏、无发热、无视力下降等并发症。肿瘤全切除率95.0%(19/20),次全切除率5.0%(1/20)。术前是否服用溴隐亭的患者手术疗效无明显影响。术后20例患者中12例PRL水平恢复至正常水平。3组患者术后PRL恢复正常率分别为100%、83.3%、12.5%。结论经单鼻孔蝶窦入路手术是治疗泌乳素腺体瘤的有效手段,其中术前PRL水平是影响手术疗效和预后的主要因素,而术前是否服用溴隐亭对手术疗效未见有明显影响。     

溴隐亭治疗垂体催乳素大腺瘤

目的 :探讨单纯溴隐亭治疗垂体催乳素大腺瘤的疗效。方法 :垂体催乳素大腺瘤 2 3例 ,用溴隐亭 7.5～ 10mg·d-1,口服 ,肿瘤愈大 ,催乳素 (PRL)水平愈高 ,则用药剂量愈大。当肿瘤缩小至直径 <1cm、PRL <10 0 μg·L-1时减至 2 .5～5mg·d-1。结果 :2 3例服药 1个月时PRL下降 (6 7± 15 ) %。服药 6个月肿瘤直径缩小 0 .4～ 0 .9cm。 12个月时 2 1例缩小0 .6～ 1.3cm ,2例肿瘤消失。 3年时复查 15例 ,有 11例肿瘤直径仅为 0 .5～ 0 .7cm ,其中 1例伴囊性变 ;3例肿瘤消失 (含上述2例 ) ;1例空蝶鞍。服药 6～ 14周停止溢乳 ,5～ 8周月经恢复。结论 :单纯溴隐亭治疗可使垂体PRL大腺瘤缩小或消失 ,且能恢复病人的生殖内分泌功能。     

麦芽提取物对高泌乳素血症大鼠脑垂体泌乳素表达及乳腺组织形态学的影响

目的：观察麦芽提取物对高泌乳素血症大鼠垂体泌乳素( PRL)表达及乳腺组织形态学的影响。方法大鼠背部皮下注射盐酸甲氧氯普胺制备高泌乳素血症模型。60只大鼠分为正常对照组、模型对照组、溴隐亭组及麦芽提取物大、中和小剂量组。除正常对照组外,其他组进行造模。溴隐亭组给予溴隐亭0.389 mg·kg-1·d-1;麦芽提取物小、中和大剂量组分别给予麦芽提取物7.98,15.96和31.92 g·kg-1·d-1。正常对照组和模型对照组给予等容量纯化水。大鼠在造模成功后,灌胃给予相应的药物进行治疗给药,每次2 mL,每日1次,连续30 d。对大鼠脑垂体PRL阳性细胞进行计数,采用反转录聚合酶链反应( RT-PCR)检测大鼠垂体PRL mRNA的表达水平,以及采用免疫组化法观察乳腺组织形态学的变化。结果正常对照组、模型对照组、溴隐亭组、麦芽提取物大、中和小剂量组的PRL阳性细胞数量分别为(2.4±0.3),(21.7±0.8),(3.8±0.5),(4.5±0.4),(6.7±0.5),(15.8±1.2)个,PRL mRNA表达水平分别为(0.31±0.02),(1.58±0.06),(0.45±0.04),(0.49±0.03),(0.61±0.04),(0.95±0.09)。与正常对照组比较,模型对照组大鼠脑垂体PRL阳性细胞数量和PRL mRNA表达水平显著增加(P<0.01),同时乳腺组织出现增生。与模型对照组比较,麦芽提取物大、中剂量组大鼠脑垂体PRL阳性细胞数量和PRL mRNA表达水平显著减少(P<0.01),而且乳腺增生明显减轻。结论麦芽提取物能有效治疗高泌乳素血症及抑制乳腺组织的增生,作用机制是其显著降低高泌乳素血症大鼠脑垂体PRL的表达。     

Casticin, a flavonoid isolated from Vitex rotundifolia, inhibits prolactin release in vivo and in vitro

Aim:

To investigate the anti-hyperprolactinemia activity of casticin, a flavonoid isolated from Vitex rotundifolia, and elucidate its molecular mechanism.

Methods:

Hyperprolactinemia (MIHP) was induced by administration of metoclopramide dihydrochloride (50 mg/kg, tid, ip, for 10 d) in SD rats and the primary pituitary cells were prepared from the pituitary glands of the SD rats. Prolactin concentrations were measured using a radioimmunoassay. Cell viability was measured using an MTT assay. The mRNA expression of estrogen receptor alpha and beta in rat pituitary cells was measured using semi-quantitative RT-PCR analysis.

Results:

The level of serum prolactin in the MIHP model group was 2.1 fold higher than that in the untreated control group (P<0.01). Casticin (10, 20, and 40 mg/kg, ip, for 7 d) reduced serum prolactin levels by 33.9%, 54.3%, and 64.7%, respectively (P<0.01). The positive control drug bromocriptine 1 mg/kg decreased the serum prolactin concentration in MIHP rats by 44.9%. 17β-Estradiol (E2) significantly increased the proliferation of pituitary cells and casticin (1 and 10 μmol/L) markedly inhibited E2-induced pituitary cell proliferation by 27.7% and 42.1%, respectively. Stimulation of pituitary cells with E2 increased prolactin secretion into the cell culture supernatants, and casticin (0.1, 1, and 10 μmol/L) significantly inhibited the prolactin release stimulated by E2 in a concentration-dependent manner. Casticin (1 and 10 μmol/L) significantly inhibited ERα mRNA expression in pituitary cells stimulated with E2 (P<0.01) but increased ERβ mRNA expression at a concentration of 10 μmol/L (P<0.01). However, casticin had no effects on proliferation and prolectin release of the unstimulated primary pituitary cells in vitro.

Conclusion:

Casticin inhibited the release of prolactin from pituitary cells of SD rats stimulated with E2 in vivo and in vitro. These effects might be related with inhibiting the ERα mRNA expression and increasing the ERβ mRNA expression.     

Bromocriptine in the treatment of secondary amenorrhoea and ovarian dysfunction in hyper- and normo-prolactinaemic patients

Summary

The clinical use of bromocriptine (2.5?mg twice daily) was investigated in 40 women attending an infertility clinic and presenting with secondary amenorrhoea (18) or with ovarian dysfunction (22) which had failed to respond to anti-oestrogen therapy. Patients in each group were sub-divided into those with raised and those with normal prolactin levels, and re-examined at 3 and 12 months after the start of treatment. The results confirmed that bromocriptine is effective in the treatment of hyperprolactinaemic states whether there is amenorrhoea or not. Moreover, in cases of ovarian dysfunction as well as of amenorrhoea where the prolactin levels were within the normal range, there was evidence to suggest that bromocriptine can be associated with a return of ovulation, although the mechanism by which it might do so still needs evaluation.     

阿立哌唑与利培酮治疗精神分裂症的临床疗效及对血清催乳素的影响

目的：比较阿立哌唑与利培酮治疗精神分裂症的临床疗效及对血清催乳素的影响。方法：2005年5月至2006年5月在我院治疗的80例精神分裂症患者，随机分为两组：阿立哌唑组（40例）和利培酮组（40例），阿立哌唑组给予阿立哌唑初始剂量10mg／d，2周末增至20～30mg／d，利培酮组给予利培酮初始剂量1mg,／d，2周末增至4—6mg／d。总疗程为8周。采用阳性和阴性症状量表（PANSS）、副反应量表（TESS）评定临床疗效及不良反应；采用化学发光法测定血清催乳素（PRL）水平。结果：经8周治疗，阿立哌唑组显效率72．5％；利培酮组显效率77、5％，两者差异无显著性（P〉0．05）。阿立哌唑组主要不良反应为：嗜睡，头痛，胃肠道反应，也可产生静坐不能，但未发现泌乳或闭经现象；利培酮组主要不良反应为：急性肌张力障碍、震颤、静坐不能、泌乳或闭经、体重增加等。利培酮组治疗8周后，血清PRL水平较治疗前明显升高，差异非常显著（P〈0．01），其中男性PRL升高3．5倍，女性PRL升高8倍；而阿立哌唑组血清PRL水平无变化。结论：阿立哌唑是一种较为安全、有效的抗精神病药物。     

Effects of dopamine d2 receptor agonists in a pituitary transplantation-induced hyperprolactinaemia/anovulation model in rats

1. In the present study, we investigated the effects of hyperprolactinaemia, induced by transplantation of anterior pituitary glands under the kidney capsule in female rats, on the relationship between serum and pituitary concentrations of the gonadotropins and on the oestrous cycle. 2. Rats with pituitary transplants showed increased serum prolactin concentrations and decreased serum concentrations of gonadotropins and increased pituitary concentrations of gonadotropins. Moreover, these rats showed persistent dioestrous and anovulation from 3 to 6 days after transplantation. 3. A single oral administration of cabergoline (at doses between 0.001 and 0.1 mg/kg) dose-dependently inhibited the elevated serum prolactin concentrations in hyperprolactinaemic rats. At 0.1 mg/kg, cabergoline induced a continuous reduction in serum prolactin concentrations for 5 days after administration. Terguride (0.1 mg/kg) and bromocriptine (10 mg/kg) also reduced serum prolactin concentrations at 1 and 3 days after administration. All three dopamine D2 receptor agonists increased serum gonadotropin concentrations and ovarian weight at 3 days after administration. 4. In rats exhibiting anovulation, a single oral administration of any one of the three dopamine D2 receptor agonists dose-dependently restored ovulation and a normal oestrous cycle appeared. Oral administration of cabergoline (0.03 mg/kg) or terguride (0.1 mg/kg) restored ovarian function and abolished the anovulation following a reduction in serum prolactin concentrations. However, bromocriptine (10 mg/kg) did not completely abolish anovulation. Following administration of terguride (0.3 mg/kg) or bromocriptine (30 mg/kg), only one normal oestrous cycle appeared; however, following cabergoline (0.1 mg/kg), two normal oestrous cycles appeared. 5. These results suggest that cabergoline has a potent and long-lasting action as a dopamine D2 receptor agonist and, thus, should be a useful drug for the treatment of galactorrhoea and hyperprolactinaemic amenorrhoea and/or anovulation in humans.     

Dopaminergic activity of some simplified ergoline derivatives

The dopamine (DA) agonist activity of new simplified ergoline derivatives (RU 27849, RU 28251, and RU 28306) was studied in comparison with bromocriptine. In contrast to bromocriptine, the three compounds were weak displacers of ³H-dihydroergocriptine or ³H-spiroperidol binding from bovine anterior pituitary or rat striatal membrane sites and weak inhibitors of prolactin secretion in anterior pituitary cells in culture. Similarly to bromocriptine, they did not induce changes in either the basal or the DA-induced stimulation of the adenylate cyclase activities. In vivo, the three derivatives, at a low dose, increased plasma prolactin levels, decreased striatal DA turnover, and increased striatal acetylcholine content, as did bromocriptine. Furthermore, in 6-OHDA-lesioned rats, these molecules, like bromocriptine, induced an intense contralateral circling behavior. From their effectiveness in these different tests, the potencies of these new ergoline derivatives can be ranked in the following order : N-propyl > N-methyl > N-H.     

溴隐亭对肝硬化患者催乳素水平的影响

目的观察溴隐亭对高催乳素肝硬化患者催乳素水平的影响。方法选取39例高催乳素肝硬化患者随机分为两组,治疗组20例,对照组19例,治疗3周。观察治疗前后两组患者的症状、体征、肝功能及催乳素水平指标的变化,评价溴隐亭对肝硬化患者高催乳素的疗效。结果治疗组降低催乳素水平指标明显优于对照组（P〈0.01）。结论溴隐亭有比较良好的降低高催乳素肝硬化患者催乳素水平的效果。     

Pharmacokinetics of a long-acting bromocriptine preparation (Parlodel LA) and its effect on release of prolactin and growth hormone

Summary The pharmacokinetics and endocrine actions of a long-acting form of bromocriptine (Parlodel) were examined in a controlled study in 10 healthy volunteers receiving a single i.m. injection of 50 mg. Six further subjects took bromocriptine 1.25 mg t.i.d. for 3 days p.o.In the subjects given the slow release preparation, the plasma bromocriptine concentrations increased sharply to a maximum of 1.65 mg/l 2 h after injection. This fast release process was followed by slow clearance with a half-life of 16 days. The substance was still detectable in plasma 35 days postinjection. Plasma prolactin (PRL) fell rapidly from a mean of 5.6 ng/ml to reach significantly lower levels at 60 and 120 min. Inhibition was maintained for up to 35 days, when plasma PRL was still significantly below the values recorded at baseline and in the control group. Plasma GH peaked at 3.6 ng/ml at 120 min and subsequently declined slowly to stabilize between 1.4 and 2.2 ng/ml for about 12 h, falling to below the 1 ng/ml limit for the remainder of the study period. In contrast, individuals receiving oral bromocriptine exhibited a significant elevation following the first dose and an equivalent increment after the morning dose on Day 3.Thus, the results show a prolonged inhibitory effect on PRL of this long-acting bromocriptine preparation in parallel with its slow plasma clearance. The stimulant effect on GH secretion is short lived, presumably due to desensitisation of specific receptors.     

癫痫患者血清催乳素的检测及其临床意义

目的 :为了研究癫痫患者下丘脑功能的改变及催乳素 ( PRL)在癫痫诊断中的临床意义。方法 :选择了 2 7例癫痫患者 ,2 5例非癫痫患者及 30例正常人作为对照组 ,分别采集其血样 ,用放射免疫法检测血清 PRL水平的变化。结果 :癫痫患者血清 PRL 水平明显高于非癫痫组及对照组 ,非癫痫组与对照组之间差异无显著性。结论 :癫痫发作对下丘脑 -垂体轴有一定影响 ,血清 PRL 升高的比率可作为癫痫鉴别诊断的一个参考指标     

Increase of rat serum prolactin by adenosine analogs and their blockade by the methylxanthine aminophylline

Summary The administration of the stable adenosine analogs N⁶-[(R)-methyl-2-phenylethyl]adenosine (R-PIA; 0.01–1.0 mg/kg i.p.) and 1-(6-amino-⁹H-purin-9-yl)-1-deoxy-N-ethyl--d-ribofuronamide (NECA; 0.01–1.0 mg/kg i.p.) caused a dose-related (NECA) or biphasic (R-PIA) increases in rat serum prolactin. The S-isomer of PIA was inactive up to 4 mg/kg i.p. The methylxanthine aminophylline (10 and 30 mg/kg i.p.) antagonized the R-PIA- and NECA-induced elevation of prolactin suggesting an adenosine receptor-mediated effect. The dopaminergic agentsl-dopa and bromocriptine antagonized the R-PIA and NECA-induced increase in serum prolactin. Haloperidol (a dopamine antagonist) and -methyl-p-tyrosine (a catecholamine synthesis inhibitor) potentiated the R-PIA-induced effects. R-PIA and NECA did not displace³H-haloperidol from rat striatal membranes nor effect in vitro prolactin release from rat anterior pituitary cells grown in culture. Based upon these findings it is postulated that R-PIA and NECA may be increasing prolactin secretion in part by inhibiting central dopamine release, although other mechanisms may also be operating.