氟中毒大鼠的垂体催乳素分泌

分别用腹腔注射氟化钠和喂饲含氟水的方法制造了大鼠亚急性和慢性氟中毒模型。以放免法测定了氟中毒情况下血清及垂体的催乳素含量。得到如下结果:①慢性氟中毒雌性大鼠血清催乳素水平降低,且呈剂量效应关系,垂体催乳素含量则升高。雄性大鼠血清催乳素水平无显著变化,但垂体催乳素含量增高,且呈现剂量—效应关系。②亚急性氟中毒大鼠血清催乳素水平显著升高,但垂体催乳素含量无显著变化。     

松花粉对D-半乳糖亚急性衰老模型大鼠下丘脑-垂体-睾丸轴的调节作用

目的 探讨松花粉的抗下丘脑-垂体-睾丸衰老作用。方法 D-半乳糖连续腹腔注射制作亚急性衰老雄性大鼠模型，分别采用放射免疫和酶联免疫法检测血清中黄体生成激素（LH）、卵泡刺激素（FSH）、胰岛素样生长因子1（IGF-1）、睾酮（T）含量以及下丘脑促性腺激素释放激素（GnRH）浓度的变化。结果 D-半乳糖所致亚急性衰老大鼠模型组LH、FSH、GnRH均明显上升，IGF-1、睾酮含量明显下降。与正常对照组比较差异显著（P〈0．01）；而经松花粉给药后LH、FSH、GnRH三者均有显著下降，IGF-1、车酮含量明显提高。结论 松花粉具有改善衰老雄性大鼠卞丘脑-垂体-睾丸轴功能紊乱的作用。     

氟对大鼠睾酮及胆固醇含量的影响

给５４只Ｗｉｓｔａｒ雄性大鼠饮水染氟，浓度分别为０．６ｍｇ／Ｌ（对照组）、１００ｍｇ／Ｌ和２００ｍｇ／Ｌ。于染氟后第２，４，６周分批处死，测血清睾酮，睾丸及肝组织胆固醇含量。结果显示，氟可致血清睾酮含量呈降低趋势；肝组织胆固醇含量降低，睾丸胆固醇含量无显著改变、表明氟对生殖系统及肝脏有一定的损伤作用。     

实验性慢性氟中毒对大鼠乳汁分泌的影响

选40日龄的雌性大鼠以150ppm的高氟水喂饲60日,造成大鼠慢性氟中毒,表现为血氟升高及门齿斑釉的出现。当大鼠100日龄时与正常雄鼠交配。研究了慢性氟中毒对乳汁分泌的影响。结果表明,实验组大鼠乳汁分泌减少,其垂体和血清催乳素水平降低,血清催乳素水平与血氟浓度呈显著负相关。这些结果提示慢性氟中毒大鼠乳汁分泌不足的可能机理是垂体催乳素分泌不足。     

天年饮对亚急性衰老大鼠睾丸生精细胞增殖与凋亡的影响

目的　观察天年饮对亚急性衰老大鼠血清超氧化物歧化酶 (SOD)活性、睾酮含量及睾丸生精细胞增殖与凋亡的影响。方法　 D-半乳糖连续腹腔注射制作亚急性衰老大鼠模型 ,检测各组大鼠天年饮灌胃前后血清 SOD的活性、睾酮的含量以及睾丸生精细胞增殖和凋亡的情况。结果　 D-半乳糖致亚急性衰老大鼠血清 SOD活性、睾酮含量及睾丸生精细胞 PCNA阳性表达率均明显下降 ,与正常组比较差异显著 (P<0 .0 1 ,P<0 .0 5) ;经天年饮灌胃后 ,三者均有明显提高。 D-半乳糖致亚急性衰老大鼠睾丸生精小管凋亡百分率及凋亡阳性细胞率均增高 ,与正常组比较差异显著 (P<0 .0 5) ;经天年饮灌胃后 ,二者均降低。结论　天年饮可显著提高亚急性衰老大鼠血清 SOD活性、睾酮含量及睾丸生精细胞 PCNA的表达水平 ,降低睾丸生精细胞的凋亡指数 ,因此 ,天年饮具有延缓性腺衰老的作用。     

感染刚地弓形虫雄性大鼠Th1/Th2细胞因子漂移对性激素的影响

目的研究弓形虫感染雄性大鼠后引起的Th1/Th2细胞因子漂移对黄体生成素(LH)、睾酮(T)水平的影响,探讨其对雄性生精细胞损伤的通路。方法选用9~10周龄雄性SD大鼠18只,随机分为健康对照组和弓形虫感染组。弓形虫感染组分为低剂量组和高剂量组2组,分别感染1×103和1×104个速殖子/只(采用腹腔注射法)。感染后第7 d,ELISA检测血清IFN-γI、L-4及NO水平,放射免疫法检测大鼠血清LH、T以及睾丸局部T水平,并对睾丸组织进行病理学观察。结果感染弓形虫雄性大鼠血清IFN-γ与NO水平较健康对照鼠显著升高(P<0.01),IL-4有一定程度升高,但IFN-γ/IL-4比值显著变大(P<0.01);血清及睾丸局部LH水平无显著变化;T水平尤其是睾丸局部T水平显著降低(P<0.01)。病理学检查感染组大鼠生精小管细胞层次混乱,初级精母细胞、次级精母细胞显著减少,管腔内精子稀少甚至管腔关闭。结论雄性大鼠感染弓形虫后,可能是由Th1细胞因子极化作为始动因素介导激素分泌异常,尤其是睾丸局部睾酮水平迅速降低,并进一步诱导生精细胞损伤和生精停滞。     

肾气丸对衰老大鼠睾丸抗氧化能力和生精细胞凋亡的影响

目的观察肾气丸对衰老大鼠睾丸抗氧化能力和生精细胞凋亡的影响。方法 Wistar大鼠分成4组,制备D-半乳糖亚急性衰老大鼠模型,分别灌胃相应剂量的肾气丸或生理盐水;6 w后,检测血清睾酮和睾丸组织超氧化物歧化酶(SOD)、丙二醛(MDA)水平及睾丸凋亡曲细精管数和凋亡细胞百分率。结果与正常组比较,模型组比较正常组,大鼠血清睾酮和睾丸组织SOD水平显著下降(P<0.01),睾丸组织MDA水平及凋亡曲细精管数和凋亡细胞百分率均显著升高(P<0.01);肾气丸可明显升高衰老模型大鼠血清睾酮和睾丸组织SOD水平(P<0.05或P<0.01),明显降低睾丸组织MDA水平及凋亡曲细精管数和凋亡细胞百分率(P<0.05,P<0.01)。结论肾气丸可通过提高衰老大鼠血清睾酮水平、增强睾丸组织抗氧化能力及降低其生精细胞的凋亡指数,发挥延缓性腺衰老的作用。     

雌性大鼠下丘脑脑啡肽含量的增龄性变化及其对血清黄体生成素水平的影响

本实验测定了老年,成年和年轻雌性Wistar大鼠下丘脑甲硫氨酸脑啡肽(MEK)、亮氨酸脑啡肽(LEK)、血清黄体生成素(LH)的含量;并于侧脑室分别注射吗啡、纳洛酮加吗啡、酚妥拉明加纳洛酮后。观察血清LH的变化。结果表明,随着增龄,下丘脑脑啡肽(EK)含量明显升高;年轻和成年大鼠血清LH水平明显高于老年大鼠。侧脑室注射吗啡后,血清LH明显下降;注射纳洛酮后再注射吗啡,血清LH明显升高;注射酚妥拉明后再注射纳洛酮,血清LH水平显著下降。本实验结果表明,EK调节LH的分泌,并且是在去甲肾上腺素参与下完成的。作者认为,大鼠下丘脑EK含量的随龄增高可能与其下丘脑—垂体—性腺轴的老化有一定的关系。     

GnRH-A对雄性大鼠睾丸内分泌功能的抑制作用

本文用大体动物实验和睾丸细胞培养两方面的研究结果证实了国产GnRH-A大剂量非脉冲性给药对雄性大鼠睾丸内分泌功能的可逆性抑制作用。它能引起血清或培液中睾酮水平下降、孕酮水平升高,造成动物精囊及前列腺重量的减轻,但对睾丸重量、曲细精管形态以及支持细胞芳香化酶活性影响不大,对动物亦无明显的副作用。上述结果提示,国产GnRH-A可能在激素依赖性疾病的治疗中发挥作用。     

慢性氟中毒授乳大鼠垂体催乳素细胞的超微结构研究

在透射电镜下观察了慢性氟中毒授乳大鼠垂体前叶催乳素细胞的超微结构变化。按其改变程度可分为三种类型:其一,大多数催乳素(PRL)细胞的结构基本正带,只核的异染色质增多,大的成熟颗粒明显多于对照组;其二,有些 PRL 细胞内线粒体增多并明显肿胀,内嵴减少或破坏,高尔基复合体的大泡增多,胞质中有大脂滴沉积;其三,有少数 PRL 细胞退化变性。同时测定血清 PRL 水平降低,垂体 PRL 含量及浓度升高。以上结果提示:慢性氟中毒可能使催乳素的释放受阻,并且氟对 PRL 细胞可能有直接的毒性作用。     

慢性氟中毒大鼠垂体生长激素细胞及下丘脑生长抑素神经元的免疫细胞化学研究

本实验对慢性氟中毒大鼠垂体生长激素(GH)细胞及下丘脑生长抑素(SS)神经元进行了免疫细胞化学染色,并用图像分析仪对GH及SS进行了半定量分析。结果表明:同对照组相比,氟中毒垂体GH细胞中的阳性反应颗粒细小并弥散地分布,半定量分析表明其GH含量明显低于对照组。未见下丘脑SS神经元及其SS含量有明显改变。本研究结果提示高氟可直接作用于垂体GH细胞影响其合成分泌功能。     

氟中毒大鼠骨骼X线动态观察及硒的影响

目的 观察氟中毒大鼠骨Ｘ线改变及硒的影响。方法 ２个组Ｗｉｓｔａｒ大鼠饮１．５８和２．６３ｍｍｏｌ／Ｌ氟水；２个组鼠饮氟水加饲２．０ｍｇ／ｋｇ硒饲料。每２个月用钼靶Ｘ线摄骨片共计６次。实验１４个月时测血、尿、骨氟。结果 氟中毒大鼠血、尿骨氟升高。骨Ｘ改变以骨盆骨结构异常出现最早，其次为腰椎、尾骨；前、后肢改变晚且较少；前肢显现骨间膜骨化，且晚于骨结构改变。实验８个月发性早期氟骨症征象。氟加硒大鼠血     

Effect of treatment with an agonist of luteinizing hormone releasing hormone on early maturational changes in pituitary and testicular function in the rat.

Male rats aged 30 days were injected once daily for between 1 and 7 days with 50 ng (D-serine t-butyl6, des-glycine-NH210) luteinizing hormone releasing hormone ethylamide (LH-RH agonist), and pituitary and testicular function were assessed. Treatment for 7 days significantly (P less than 0.02) inhibited maturational increases in the pituitary content and serum concentration of gonadotrophins, testicular luteinizing hormone (LH)-receptor concentration and the testicular capacity to secrete testosterone; the pituitary content and serum concentration of prolactin, the hypothalamic content of LH-RH and testicular weight were unaffected. In rats treated with LH-RH agonist, the initial (2 to 3 days) reduction in testicular LH-receptors and the capacity to secrete testosterone probably resulted from acutely raised levels of LH in the blood, whilst later effects may have resulted from the apparently chronic reduction in serum gonadotrophin levels. The latter may reflect a decrease in pituitary responsiveness to repeated stimulation with LH-RH agonist. Despite the extensive loss of testicular LH-receptors and diminished responsiveness, the concentration of HCG which significantly (P less than 0.05) increased testosterone secretion by the testis in vitro was the same (2 pmol/l) as that for testes from control rats.     

Relationship of changes in serum concentrations of prolactin and testosterone during dopaminergic modulation in males

To evaluate the effect of PRL on the male pituitary-gonadal system, serum concentrations of PRL, testosterone, LH and FSH were determined in healthy young men daily before, during, and after 3-day oral administration of bromocriptine, metoclopramide or sulpiride. Bromocriptine (2.5 mg as a single dose) caused, concurrently with a marked suppression of serum PRL, a significant increase of serum testosterone and a transient decrease of serum LH. The changes of PRL and testosterone were negatively correlated. With metoclopramide (10 mg q.i.d.) serum PRL was increased and testosterone inversely decreased. There was no change in LH and FSH. Sulpiride (50 mg q.i.d.) evoked the elevation of serum PRL and LH, but no change in testosterone. A significant increase in serum concentration of testosterone was also observed in a patient with PRL-producing pituitary tumour and four out of seven patients with acromegaly during bromocriptine treatment. These results suggest an inhibitory effect of PRL on testosterone secretion at the gonadal level, or direct dopaminergic stimulatory control of testosterone secretion.     

Effects of Alcohol on β-Endorphin and Reproductive Hormones in the Male Rat

In an attempt to examine the relationship between alcohol-induced alterations in immunoreactive beta-endorphin (i-beta E) levels in the hypothalamic-pituitary-gonadal axis and the synthesis and release of reproductive hormones, male rats were treated with either an acute intraperitoneal injection of alcohol or were chronically exposed to an alcohol-containing liquid diet. Hypothalamic, pituitary, serum, and testicular levels of immunoreactive beta-endorphin (i-beta E) and serum levels of luteinizing hormone (LH) and testosterone were measured at various times after initiation of these treatments. Testicular interstitial fluid (TIF) volumes and levels of TIF i-beta E and testosterone were also measured 4 hr after acute treatment as an index of testicular release of these substances. Acute alcohol decreased pituitary levels of i-beta E and increased serum levels of the peptide for up to 1 hr after its injection, but did not alter hypothalamic or testicular levels. Acute alcohol markedly increased TIF i-beta E and decreased TIF testosterone and TIF volume. Sharp decreases in serum LH and testosterone were observed in association with these acute changes in i-beta E levels in the pituitary, blood, and testes. During chronic alcohol exposure serum testosterone levels were substantially depressed, but tolerance appeared to develop quickly to the chronic effects of alcohol on serum LH. Similarly, tolerance to alcohol's effects on i-beta E levels in the pituitary and serum also appeared to develop during chronic alcohol administration. However, hypothalamic and testicular i-beta E levels were markedly suppressed by chronic alcohol administration in contrast to the lack of effect observed after acute alcohol administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

慢性氟中毒大鼠脑组织中c-Jun氨基末端激酶表达水平观察

目的 观察慢性氟中毒大鼠脑组织中c-Jun氨基末端激酶(JNK)信号转导激酶表达变化,进一步揭示慢性氟中毒神经损伤的分子机制.方法 SD大鼠随机分为3组:对照组、低氟组、高氟组,每组24只,饮用水含氟量分别为＜0.5和5.0、50.0 mg/L,实验期为6个月.用氟离子选择电极法测定大鼠尿氟及血氟,用Western blotting和免疫组织化学方法检测脑组织中JNK信号转导激酶的表达和分布,并分析血氟与活化的JNK激酶的相关关系.结果低氟组和高氟组大鼠尿氟[(2.56±0.91)、(5.73±3.14)mg/L]和血氟[(0.36±0.14)、(0.50±0.18)mg/L]均较对照组[(0.92±0.30)、(0.12±0.07)mg/L]升高(P均＜0.05).高氟组(1.74±0.69)脑组织phospho-JNK表达高于对照组(1.00±0.37)和低氟组(1.20±0.28,P均＜0.05);total-JNK蛋白表达水平3组间比较,差异无统计学意义(F=0.046,P＞0.05).phospho-JNK、total-JNK阳性表达神经元主要集中在皮质、海马和背侧丘脑,其中高氟组大鼠phospho-JNK在顶叶皮质(119.3±14.1)、枕叶皮质(112.7±5.4)、海马CA3区(100.6±8.9)、背侧丘脑(117.8±10.4)及橄榄核(112.6±5.9)中阳性表达较对照组(104.1±8.9、106.6±9.6、106.6±9.7、108.9±6.4、100.3±8.4)和低氟组(96.7±17.1、102.5±8.3、106.4±6.5、110.2±9.3、102.4±4.7、102.5±9.8)明显增高(P均＜0.05),而total-JNK在各组大鼠脑组织中阳性表达分布未见明显改变(P均＞0.05).相关分析结果发现,随大鼠血氟升高,脑组织中phospho-JNK表达呈增高趋势,二者存在正相关关系(r=0.677).结论慢性氟中毒导致脑组织中磷酸化JNK表达改变,并与机体中氟蓄积量存在相关关系,这些改变可能与慢性氟中毒导致的神经损伤有关系.     

实验性慢性氟中毒大鼠垂体生长激素细胞的超微结构及酶细胞化学研究

本实验以饮用含100mg/L高氟水的方法复制了雄性大鼠实验性慢性氟中毒模型。用透射电镜观察了高氟对大鼠垂体生长激素(GH)细胞及其硫胺素焦磷酸酶(TPPase)活性的影响。结果表明:氟中毒大鼠垂体中大多数GH细胞的细胞器不如对照组发达;线粒体有破坏,基质密度增高,出现空泡或嵴减少;溶酶体增多,分泌颗粒数量增多但较小,说明GH细胞处于机能不活跃状态。电镜酶细胞化学研究结果显示氟中毒大鼠垂体GH细胞的TPPase活性受到抑制。结果提示高氟可能抑制垂体GH细胞的TPPase活性并影响其超微结构。     

氟中毒大鼠血清皮质酮含量的变化

本文观察了氟中毒大鼠血清皮质酮含量变化。发现在不同的实验条件下,氟中毒大鼠血清皮质酮含量均明显降低。认为在氟,糖皮质激素以及骨和胶原代谢之间一定存在某种联系,而这种联系可能在氟中毒的发病机制中占重要地位。     

cis-platinum-mediated decrease in serum testosterone is associated with depression of luteinizing hormone receptors and cytochrome P-450scc in rat testis

Previously we had shown that cis-platinum decreases testosterone levels in rat serum and that hCG reverses this effect. The purpose of these studies was to determine the biochemical basis of cis-platinum-mediated effects on testicular testosterone production. In the testis of rats treated with cis-platinum (7 mg/kg, iv), the mitochondrial P-450scc concentration and side-chain cleavage activity were depressed by 40%. Also, the microsomal 17 alpha-hydroxylase activity and cytochrome P-450 concentration were decreased. Testicular binding capacity (in vitro) for [125I]hCG was decreased by 75-80%. On the other hand, FSH binding to Sertoli cell membrane receptors was not appreciably changed. hCG (25 IU/100 g daily) in treated rats caused complete occupancy of the remaining 20-25% LH receptors and caused a 20- to 30-fold increase in serum and testicular testosterone, a 2-fold increase in mitochondrial P-450scc, and a 5-fold acceleration of side-chain cleavage activity. 17 alpha-Hydroxylase activity and microsomal cytochrome P-450 were not increased over the control values. In addition to testicular functions, pituitary glycoprotein hormone production was assessed. Treatment of rats with cis-platinum (7 mg/kg, iv) did not change serum LH or FSH, but caused a 50% decrease in serum and testicular testosterone levels. A GnRH challenge test (1.5 micrograms/100 g, in 30 min) of treated rats caused prompt increases of 10- to 15-fold in serum LH and resulted in increases in serum and testicular testosterone. Thus, there was little evidence for cis-platinum effects at the level of hypothalamus or pituitary that could account for the decreased testosterone production. Reversal of the cis-platinum effect on steroidogenesis by hCG or GnRH appears to be due to the induction of suprasaturating levels of LH with full occupancy of remaining Leydig cell LH receptors. This, in turn, would reverse the diminished levels of mitochondrial side-chain cleavage activity and cytochrome P-450scc. These data suggest that cis-platinum causes a depression in serum testosterone, mainly by decreasing the number of LH receptors and inhibiting side-chain cleavage activity.     

Effects of monoamine neurotoxins injected in different brain areas on gonadotropin and androgen secretion in the male

In order to investigate the relative contribution of the serotoninergic and catecholaminergic innervation of different brain structures to the control of gonadotropin secretion in the male, adult rats were given bilateral injections of the selective neurotoxins, 5,7-dihydroxytryptamine and 6-hydroxydopamine, into the mediobasal hypothalamus, the medial preoptic area, the amygdala, and the medial forebrain bundle. Serum levels of luteinizing hormone (LH), follicle-stimulating hormone, testosterone, pituitary follicle-stimulating hormone, and LH content were measured 15 days later. The medial preoptic area 5,7-dihydroxytryptamine injections were followed by 2- to 3-fold increases of serum LH and testosterone levels and pituitary LH concentration. The 6-hydroxydopamine injections in the medial forebrain bundle resulted in a 60% decrease of pituitary LH content, associated with serum levels of LH and testosterone which were lowered, although not significantly. None of the treatments seemed to influence either serum or pituitary concentrations of follicle-stimulating hormone. These results suggest a hitherto undocumented major function of the serotoninergic innervation of the medial preoptic area in the control of LH secretion in the male and confirm previous reports indicating that some of the catecholaminergic fibers carried by the medial forebrain bundle can be modulatory for LH secretion.