脑室注射γ-氨基丁酸对雄性大鼠下丘脑促性腺激素释放激素含量的影响

本研究观察了不同剂量γ－氨基丁酸（ＧＡＢＡ）对雄性大鼠下丘脑促性腺激素释放激素（ＧｎＲＨ）含量的作用。结果表明，脑室注射５、５０、２５０及５００ｍｍｏｌ／ＬＧＡＢＡ各为２０μｌ，４０分钟后下丘脑ＧｎＲＨ含量分别为３．５７±０．５８、３．７５±０．６６、４．６３±０．６３及５．０７±０．５９ｎｇ／１０ｍｇ湿重组织，均显著高于对照组下丘脑ＧｎＲＨ含量（１．７６±０．２１ｎｇ／１０ｍｇ湿重组织，Ｐ＜０．０５）。脑室注射２５０ｍｍｏｌ／ＬＧＡＢＡ２０μｌ后２０、４０、６０、１２０及２４０分钟下丘脑ＧｎＲＨ含量依次为２．２４±０．２９、４．６３±０．６３、５．１１±０．３８、４．２０±０．４０及３．９８±０．９１ｎｇ／１０ｍｇ湿重组织。ＧＡＢＡ受体拮抗剂荷包牡丹碱（ｂｉｃｕｃｕｌｉｎｅ，Ｂｉｃ）可阻断ＧＡＢＡ对下丘脑ＧｎＲＨ含量的促进作用。     

脑室注射血管紧张素Ⅱ对雄性大鼠下丘脑促性腺激素释放激素含量？…

本实验观察了脑室注射血管紧张素Ⅱ（ＡⅡ）地成年雄性Ｗｉｓｔａｒ大鼠下丘脑促性腺激素素释放激素含量的影响。摘取下丘脑组织，匀浆化，用放射免疫分析检测奖交涉 清中ＧｎＲＨ的含量，结果表明，脑室注射ＡⅡ后６０、９０及１２０分钟，下丘脑ＧｎＲＨ含量分别为２．８８±０．４７、２．６９±０．３８及２．５４±０．５５ｎｇ／１０ｍｇ湿重组织，均显著高于盐水对照组，提示ＡⅡ可促进雄性大鼠下丘脑ＧＮＲＨ的生成。     

白介素—2对大鼠下丘脑和血浆促性腺激素释放激素水平的影响

本研究运用放射免疫分析观察腹腔内注射不同剂量白介素－2（1000U、2000U）的雄性SD大鼠下丘脑和血浆中促性腺激素释放激素（LHRH）以及血清睾酮的含量变化。结果显示：①下丘脑LHRH水平呈下降趋势，但与对照组相比无统计学意义；②血浆LHRH水平下降，与对照组相比无显著性差别；③血清睾酮含量低于对照组，只有高剂量的1IL－2有明显差别；结果提示：IL－2可抑制下丘脑LHRH的分泌，降低血中睾酮水平。     

促性腺激素释放激素激动剂降调节对促性腺激素阈值的影响

1983年Porter等[1]将促性腺激素释放激素激动剂(GnRH-a)引入可控制性诱导排卵方案获得成功,并提出GnRH-a降调节概念.由于GnRH-a较天然GnRH-a具有更高的受体亲和力和抵抗酶降解能力,在注射后短期内先出现垂体激发作用,产生一过性升高(flare up)效应,并促使血清促性腺激素(Gn)水平暂时性升高;随后表现为持续的垂体-卵巢轴抑制效应,即垂体-卵巢轴降调节作用(down regulation).表现为GnRH-a脉冲式分泌节奏消失,Gn合成与释放显著减少,血清卵泡刺激素(FSH)、黄体生成素(LH)水平降低不足以维持卵泡发育,雌、孕激素达到绝经期水平,这是一种可逆的、以LH、雌二醇(E-2)水平为主的垂体降调节作用.     

促性腺激素释放激素及其类似物的研究进展

促性腺激素释放激素 (GnRH) ,是由下丘脑分泌的十肽激素 ,其受体为钙离子动员受体。GnRH脉冲式释放刺激垂体促性腺激素的合成和分泌从而调节性激素的分泌 ,是性腺轴系的原动力 ,此外对性腺还可能具有直接作用。对GnRH分子结构修饰而合成的结构类似物 ,已经在生殖内分泌疾病治疗、计划生育等方面得到应用。     

促性腺激素释放激素类似物在妇科的应用研究进展

促性腺激素释放激素(GnRH)由下丘脑分泌,刺激或抑制垂体促性腺激素的分泌,有相当的活性潜能。在治疗妇科肿瘤、子宫内膜异位症、特发性真性性早熟以及辅助生殖技术中广泛应用,本文对其在妇科的应用现状进行综述。     

促性腺激素释放激素激动剂降调节的个体化与促性腺激素启动日时机选择

促性腺激素释放激素激动剂(GnRH-a)已经广泛地应用于体外受精(IVF)垂体降调节中.GnRH-a分长效和短效两种剂型,长效剂型患者接受性和依从性高,但有卵巢过度抑制倾向,会造成促性腺激素(Gn)用量增加、使用时间延长,因而增加经济负担,而短效者可接受性和依从性较差.两者临床效果无显著差异.临床上常用的GnRH-a降调节方案有长、超长、短、超短等方案,各种方案的临床效果总体上并无显著差异但各有优缺点,通常卵巢功能减退的患者建议给予短方案,甚至超短方案,而卵巢储备功能正常患者常用长方案.超长方案对于合并子宫内膜异位症或多囊卵巢综合征患者等能提高临床妊娠率.降调标准存在争议,因此文献报道对于Gn的启动时间亦有不同,需要根据患者个体及不同的降调节方案而定.适当延迟启动时间可能改善卵母细胞的质量和内膜接受性,从而提高临床妊娠率,而且适当推迟Gn启动时间对于减少Gn的用量,降低患者的经济负担也是十分有益的.     

促性腺激素释放激素抑制剂与促性腺激素释放激素激动剂用于IVF-ET中正常反应患者的系统性评价及Meta分析

目的系统性评价促性腺激素释放激素拮抗剂(GnRH-ant)与促性腺激素释放激素激动剂(GnRH-a)长方案用于体外受精-胚胎移植(IVF-ET)中正常反应患者促排卵治疗的有效性及安全性。方法计算机检索6种数据库,时间截止至2014年12月底。纳入GnRH-ant与GnRH-a用于卵巢正常反应患者治疗的随机对照试验(RCT),采用Revman5.1软件进行Meta分析。结果 24篇RCT符合纳入标准。刺激天数(MD:-0.70,95%CI:-1.08~-0.32)、Gn用量(MD:-2.94,95%CI:-4.9~-0.97)、HCG日E2值(MD:-353.75,95%CI:-530.60~-176.90)、获卵数(MD:-1.32,95%CI:-2.00~-0.64)、临床妊娠率(OR:0.87,95%CI:0.75~1.00)、OHSS率(OR:0.57,95%CI:0.41~0.79)GnRH-ant组显著低于GnRH-a长方案组(P0.05),但是HCG日子宫内膜厚度(MD:-0.07,95%CI:-0.25~0.12)、持续妊娠率(OR:0.88,95%CI:0.75~1.03)、活产率(OR:0.90,95%CI:0.70~1.17)、流产率(OR:1.18,95%CI:0.86~1.62)、周期取消率(OR:1.10,95%CI:0.89~1.35)两组差异无统计学意义(P0.05)。结论在正常反应患者行IVF-ET治疗中,GnRHant方案较之GnRH-a标准的长方案显著降低卵巢过度刺激综合征(OHSS)发生率,持续妊娠率、活产率相似。     

促性腺激素释放激素激动剂降调对垂体内外的影响

降调是促激素下调自身的受体以调节靶组织对激素的反应性,是促激素调节其自身作用的机制之一.除受体的升调和降调外,促激素还可通过自分泌/旁分泌、激素的异质性来调节自身的作用.降调的机制是通过受体与调节亚单位G蛋白解耦联、受体内在化进入细胞、以及腺苷酸环化酶的调节和催化亚单位解耦联3种途径来实现的.降调对卵泡刺激素(FSH)和黄体生成素(LH)的直接作用是使40％～60％的FSH分泌受到抑制,而90％的LH分泌受到抑制,目的是抑制过早内源性LH峰.降调对FSH、LH旁分泌调节的作用需要通过FSH和LH发挥作用,旁分泌调节因子本身并没有促使卵泡发育的作用.由于类固醇激素的负反馈是通过下丘脑垂体发挥作用,而降调是在促性腺激素释放激素(GnRH)的受体水平,因此取消了类固醇激素正常的正负反馈.由于卵巢颗粒细胞、膜细胞、黄体细胞均有GnRH受体,理论上推测GnRH对卵巢可能有直接作用.动物实验及体外试验均提示GnRH对卵巢颗粒细胞有直接作用,体现在类固醇的合成和卵泡的发育两方面.因此,促性腺激素释放激素激动剂(GnRH-a)提高妊娠率的作用除了来自于抑制过早LH峰,降低过高LH的不利作用外,还可能来自GnRH-a对卵泡发育、卵母细胞成熟、子宫内膜的容受性等直接作用,但目前的研究方法尚无法证实.     

MAPK and angiotensin II receptor in kidney of newborn rats from losartan-treated dams

Several lines of evidence suggest that angiotensin II (A-II) participates in the postnatal development of the kidney in rats. Many effects of A-II are mediated by mitogen-activated protein kinase (MAPK) pathways. This study investigated the influence that treatment with losartan during lactation has on MAPKs and on A-II receptor types 1 (AT(1)) and 2 (AT(2)) expression in the renal cortices of the offspring of dams exposed to losartan during lactation. In addition, we evaluated the relationship between such expression and changes in renal function and structure. Rat pups from dams receiving 2% sucrose or losartan diluted in 2% sucrose (40 mg/dl) during lactation were killed 30 days after birth, and the kidneys were removed for histological, immunohistochemical, and Western blot analysis. AT(1) and AT(2) receptors and p-p38, c-Jun N-terminal kinases (p-JNK) and extracellular signal-regulated protein kinases (p-ERK) expression were evaluated using Western blot analysis. The study-group rats presented an increase in AT(2) receptor and MAPK expression. In addition, these rats also presented lower glomerular filtration rate (GFR), greater albuminuria, and changes in renal structure. In conclusion, newborn rats from dams exposed to losartan during lactation presented changes in renal structure and function, which were associated with AT(2) receptor and MAPK expression in the kidneys.     

血管紧张素II及其受体在人卵巢的表达

目的　探讨卵巢血管紧张素II(AngII)及其受体 (AT1、AT2 )在人卵巢的表达与分布。　方法　免疫组化法检测33份人卵巢组织标本中AngII及其受体AT1、AT2的表达与分布。　结果　AngII及受体AT1、AT2在卵巢的分布基本一致 ,三者在卵母细胞均有表达 ,大卵泡尤其是排卵前卵泡的颗粒细胞含量丰富 ,卵泡膜细胞几无表达 ;颗粒黄体细胞与膜黄体细胞三者含量均丰富 ,并伴随黄体退化而消失。　结论　AngII及其受体可在人卵巢局部生成 ,并存在于同一种细胞内 ,提示它们可能以自分泌方式参与卵巢功能的调节。     

Human growth hormone and growth hormone releasing hormone: A double-masked,placebo-controlled study of their effects on bone metabolism in elderly women

We treated 42 postmenopausal women with decreased bone mass for 12 weeks with human growth hormone, growth hormone releasing hormone, or placebo. Bone density and biochemical markers were determined before and during treatment, and 4 weeks after withdrawal. Biochemical markers of bone formation and resorption increased significantly in the group treated with growth hormone, whereas no changes were seen in the other groups. After withdrawal of therapy the bone markers declined without reaching baseline values. Bone density in the forearm, spine and proximal femur was unchanged in all groups. We conclude that treatment with growth hormone stimulates bone metabolism in elderly postmenopausal women with decreased bone mass.     

Growth hormone response to acute growth hormone releasing hormone administration in uraemic patients on haemodialysis.

To examine the response of growth hormone (GH) to growth hormone releasing factor (GHRF) in patients on haemodialysis, we performed the acute GHRF test (50 micrograms administered intravenously as a bolus) in 10 uraemic male patients on haemodialysis and eight normal controls. Each patient was tested before and after a haemodialysis session (at 08.30 and 12.30). Controls were tested on the same time schedule. At 08.30, patients had significantly greater basal and peak GH values (2.5 +/- 0.6 and 27.8 +/- 5.5 micrograms/l) than controls (0.68 +/- and 11.5 +/- 4 micrograms/l). After the haemodialysis session, basal and peak values declined significantly (P less than 0.01) in the uraemic group (0.5 +/- 0.03 and 3.1 +/- 1.1 micrograms/l), whereas the controls did not show such a change in the 12.30 test. Basal and intratest glycaemic values were comparable both before and after haemodialysis. After dialysis test results did not change either with the use of glucose-free dialysate or with bicarbonate buffer. Uraemic patients display a greater GH response to GHRF injection than normal subjects, and this response decreases after haemodialysis. The degree of reduction has no relationship with either glycaemia or the dialysate buffer. We suggest that other GH secretion regulating factors are altered by the haemodialysis procedure.     

Different role of angiotensin II type 1 and type 2 receptors in renin release by interaction of angiotensin II and renal sympathetic nerve

Background. Angiotensin II (Ang II) is involved in the direct inhibition of renin release from juxtaglomerular (JG) cells in the kidney as the negative feedback loop of the renin-angiotensin system. Ang II also modulates renin release via the sympathetic nervous system, since the renal sympathetic nerves stimulate renin release, and the interaction of the sympathetic nervous system with Ang II has been demonstrated to occur at multiple levels. Methods. Experiments were performed in conscious unrestrained rabbits. Ang II (1.0 ng/kg per min) was infused intravenously for 60 min in renal-denervated (Dx; n = 6) and sham-denervated (Sh; n = 6) rabbits, and plasma renin activity (PRA) was determined. Then the intrarenal administration of the Ang II type-1 receptor (AT1R) antagonist, losartan, or type-2 receptor (AT2R) antagonist, PD123319 was carried out, during infusion of Ang II or saline in both Dx and Sh. Results. PRA was decreased in both Sh (5.9 ± 0.6 to 2.8 ± 0.7 ng/ml per h; n = 6, P < 0.01) and Dx (5.7 ± 0.4 to 3.8 ± 0.6 ng/ml per h; n = 6, P < 0.01) during Ang II infusion. The degree of decrease was significantly less in Dx than in Sh (P < 0.05), indicating that the inhibition of renin release by Ang II is associated with renal nerves. The intrarenal administration of losartan in Sh significantly decreased PRA produced by Ang II (5.6 ± 0.3 to 4.8 ± 0.3 ng/ml per h; n = 6, P < 0.05) vs. saline vehicle (5.7 ± 0.3 to 2.8 ± 0.2 ng/ml per h; n = 6, P < 0.01) (P < 0.05). Blockade with losartan in Dx significantly increased PRA (5.8 ± 0.4 to 6.6 ± 0.4 ng/ml per h; n = 6, P < 0.05) during the infusion of Ang II. Renin response to the Ang II infusion was not influenced by the intrarenal administration of PD123319 alone, in either Sh or Dx. Conclusion. Ang II appears to facilitate sympathetic neurotransmission through the postjunctional AT1R leading to renin release. Received: August 12, 1998 / Accepted: October 9, 1998     

正常卵巢与多囊卵巢组织血管紧张素II的免疫组化定位

对２０ 例多囊卵巢综合征（ＰＣＯＳ）患者及１２ 例正常育龄妇女的卵巢组织进行血管紧张素ＩＩ的免疫组织化学定位,观察其在卵巢组织的分布情况。结果：正常卵巢组织,卵泡期血管紧张素ＩＩ在卵泡膜细胞为弱阳性染色;颗粒细胞只有近排卵期的优势卵泡呈强阳性反应,并持续至整个黄体期;基质为弱阳性或阴性染色。多囊卵巢组织血管紧张素ＩＩ定位无此波动节律,并以卵泡膜细胞和基质弥漫性强阳性反应为特点。结果提示,血管紧张素ＩＩ参与卵泡发育、排卵、黄体形成和多囊卵巢的病理改变     

1型血管紧张素Ⅱ受体拮抗剂抑制大鼠胰腺纤维化形成

目的探讨1型血管紧张素Ⅱ受体(AT1)拮抗剂洛沙坦对大鼠实验性胰腺纤维化形成的抑制作用。方法胰管内注射2％三硝基苯磺酸(TNBS)诱导大鼠胰腺纤维化模型。于制模后第2天，治疗组给予洛沙坦(10mg／kg体重)灌胃，每日1次，对照组给予等容积的无菌蒸馏水。于制模后3，7，14，21．28d分别处死两组大鼠(每时点各6只)，并留取血清和胰腺组织。通过HE染色和Van Gieson(V-G)染色观察胰腺组织病理学改变和细胞外基质胶原纤维分布。分别应用放射免疫法和酶动力法测定血清透明质酸(HA)和淀粉酶。胰腺组织AT1受体蛋白和mRNA表达分别采用免疫组化和逆转录-聚合酶链式反应(RT-PCR)方法。结果洛沙坦可抑制TNBS诱导的大鼠胰腺纤维化形成，降低胰腺组织炎症细胞浸润、腺泡细胞坏死及纤维化程度，并且能降低血清HA和淀粉酶水平、下调AT1受体基因和蛋白的表达。结论1型血管紧张素Ⅱ受体拮抗剂对TNBS诱导的大鼠胰腺纤维化形成具有抑制作用，表明肾素-血管紧张素系统(RAS)在慢性胰腺炎胰腺纤维化的发生发展过程中起重要的介导调节作用。