海洛因与吗啡依赖恒河猴的病理组织学研究

目的··：比较海洛因与吗啡恒河猴依赖模型。方法··：利用光镜对恒河猴海洛因及吗啡依赖形成过程中垂体、睾丸、肾上腺等器官组织进行病理形态观察。结果··：在注射海洛因３个月内,垂体从无明显病变转为个别嗜酸性细胞坏死到部分嗜酸性和嗜碱性细胞坏死;下丘脑从无明显病变转为少数神经细胞坏死;肾上腺从无明显病变转为个别束状带细胞水肿到大多数束状带细胞水肿;睾丸从无明显病变转为个别曲细精管萎缩,见成熟精子和间质细胞到大部分曲细精管萎缩到全部曲细精管萎缩,无成熟精子和间质细胞,且自然戒断３个月时垂体、睾丸的病变未得到恢复。注射吗啡３个月时,垂体仅有个别嫌色细胞水肿;下丘脑结构基本正常;睾丸仅为部分曲细精管萎缩,有成熟精子;肾上腺个别束状带细胞水肿,且自然戒断３个月时病变已恢复。结论··：海洛因依赖猴造成垂体、睾丸、肾上腺等组织器官损伤的程度比吗啡依赖猴的更重;在恒河猴海洛因依赖形成过程中,随注射时间延长,组织损伤程度加重。     

复方中药康赛德对海洛因依赖猴血清睾酮及睾丸结构病理变化的疗效观察

目的··:探讨海洛因依赖恒河猴经复方中药康赛德戒断治疗后睾丸结构和功能的恢复情况。方法··:HE染色 ,光镜观察。结果··:在海洛因依赖形成过程中 ,生理盐水对照组(NS组)和康赛德治疗组(CDC组)睾丸均逐渐萎缩变小 ,血清睾酮水平渐进性下降。NS组自然戒断后 ,睾丸体积虽有所恢复 ,但血清睾酮水平持续性下降。自然戒断3个月时 ,睾丸曲细精管全部萎缩 ,成熟精子少或无 ,间质细胞减少或消失 ,间质纤维组织明显增生。在CDC组 ,康赛德治疗后 ,睾丸体积迅速恢复 ,明显大于对照组 (P<0.05) ,血清睾酮水平回升至正常或接近正常(与NS组相比 ,P<0.05)。治疗3个月时 ,睾丸结构基本正常或仅为部分曲细精管萎缩 ,成熟精子较多 ,并可见间质细胞。结论·· :复方中药康赛德能帮助海洛因依赖猴速度更快、程度更佳地恢复睾丸的结构和功能     

海洛因及吗啡对恒河猴β-内啡肽、促肾上腺皮质激素、皮质醇、睾酮的影响

本文用放射免疫法对海洛因、吗啡依赖性恒河猴依赖形成前、后及戒断过程中,血中β-内啡肽(β-EP)、促肾上腺皮质激素(ACTH)、皮质醇、睾酮的浓度进行测定,以比较海洛因及吗啡对恒河猴下丘脑-垂体-肾上腺及性腺组织的影响是否一致.结果表明:(1)海洛因对β-EP的抑制强度大于吗啡;(2)海洛因对下丘脑-垂体-肾上腺轴(HPA轴)的损害程度比吗啡重;(3)海洛因组睾酮分泌的受抑程度大于吗啡组.因此,海洛因对下丘脑-垂体-肾上腺及性腺轴的损伤程度比吗啡严重.     

海洛因及吗啡对恒河猴β—内啡肽,促肾上腺皮质激素,皮质醇 …

本文用放射免疫法海洛因,吗啡依赖性恒河猴依赖形成前,后及戒断过程中,血中β－内啡肽,保肾上腺皮质激素,皮质醇,睾酮的逍度进行测定,以比较洛洛因及吗啡对恒河猴下丘脑－垂体－肾上腺及性腺组织的影响是否一致;结果透明：（１）海洛因对β－ＥＰ的抑制强度大于吗啡;（２）海洛因对下丘脑－垂体－肾上腺的损害程度比吗啡重;（３）海洛因组睾酮分泌的受抑程度大于吗啡组。     

海洛因及吗啡对恒河猴β-内啡肽、促肾上腺皮质激素、皮质醇、睾酮的影响海洛因及吗啡对恒河猴β-内啡肽、促肾上腺皮质激素、皮质醇、睾酮的影响

本文用放射免疫法对海洛因、吗啡依赖性恒河猴依赖形成前、后及戒断过程中,血中β－内啡肽（β－ＥＰ）、促肾上腺皮质激素（ＡＣＴＨ）、皮质醇、睾酮的浓度进行测定,以比较海洛因及吗啡对恒河猴下丘脑－垂体－肾上腺及性腺组织的影响是否一致。结果表明：（１）海洛因对β－ＥＰ的抑制强度大于吗啡;（２）海洛因对下丘脑－垂体－肾上腺轴（ＨＰＡ轴）的损害程度比吗啡重;（３）海洛因组睾酮分泌的受抑程度大于吗啡组。因此,海洛因对下丘脑－垂体－肾上腺及性腺轴的损伤程度比吗啡严重。     

海洛因和吗啡对猴的致依赖性比较

本文用吗啡依赖猴作对比,对恒河猴海洛因依赖形成的时间、累计剂量、催促实验戒断反应的量 -效、时 -效变化及自然戒断反应出现的时 -效关系等进行了研究。结果表明 :海洛因sc恒河猴,起始剂量为2.5mg·kg-1 ,tid ,每2d递增1.25mg·kg-1,日剂量达11.25mg·kg-1 后,改为每日递增1.25mg·kg-1,日剂量达到20mg·kg-1 时,维持该剂量到用药时间为3mon。给药d5,当海洛因累计剂量为17.5mg·kg-1 时,催促实验中,猴出现明显的戒断症状,以后随给药剂量的增加,戒断反应呈显著的量 -效、时 -效变化,反应强度在给药头10d内增加最快,以后呈缓慢上升的趋势。注射满3mon,突然停药,可出现明显的戒断症状,其时 -效关系与吗啡组基本一致。与吗啡组相比,在依赖形成初期,海洛因具有形成依赖时间短,用药量少,戒断反应程度严重,戒断症状稍有不同,有兴奋表现等特点。海洛因组Emax=100分,ED50 =20.9mg·kg-1;吗啡组Emax=104.2分,ED50 =80.7mg·kg-1,二者的等效剂量比为1∶3.9。自然戒断实验中,二组均达最大反应强度,且戒断反应程度基本相近。     

海洛因依赖及戒断后雄性大鼠性腺轴组织病理学研究

规律腹腔注射海洛因建立♂大白鼠海洛因身体依赖模型（ｎ＝１５），戒断后制成戒断模型（ｎ＝１０），并设对照组。对依赖组和戒断组大鼠的大脑、下丘脑、垂体、肾上腺、睾丸和附睾组织做光镜和电镜观察，结果发现依赖组的大脑皮质、下丘脑、垂体、睾丸和附睾均有明显的组织病理改变及超微结构改变，且短期戒断后这些改变仍持续存在。该文对海洛因依赖引起中枢神经系统及下丘脑－垂体－睾丸轴组织产生病理改变的机理作了探讨。     

海洛因依赖者自然戒断过程中内分泌激素含量变化的研究

目的··:研究海洛因依赖者自然戒断过程中内分泌激素含量的动态变化。方法··:用放免法测定28例海洛因依赖者在自然戒断的d1、d3、d10、d30血清TSH、T3 、T4 、FSH、睾酮(Tst)、醛固酮和胰岛素含量。结果··:海洛因依赖者在自然戒断的d1、d3血清TSH、T3 、胰岛素含量均低于正常组(P<0.01) ,醛固酮含量高于正常组(P<0.05或0.01) ,T4 、FSH和Tst含量与正常组无差异。自然戒断的d10,除血清T3 、T4 含量低于正常组外(P<0.01) ,其余各激素含量与正常组已无差异。自然戒断的d30,T4 、胰岛素含量低于正常组(P<0.05或0.01) ,FSH、醛固酮含量高于正常组(P<0.05) ,TSH、T3 、Tst含量与正常组无差异。结论··:海洛因依赖者在自然戒断的d10其内分泌功能已基本恢复正常 ,但一些激素即使在戒断的d30仍有异常变化 ,提示应加强稽延性戒断症状的控制 ,以利于康复     

褪黑素对吗啡戒断小鼠前列腺和睾丸的组织学影响

目的··:观察褪黑素 (melatonin,MT)对吗啡戒断小鼠前列腺及睾丸的组织学影响。方法··:设立对照组 (A)和实验组 (B、C、D) ,实验组分别皮下注射定量吗啡 ,建立吗啡依赖模型 ,A组皮下注射等量生理盐水 ,B组继续注射吗啡 ,C组自然戒断 ,D组自然戒断后给MT。实验后将前列腺及睾丸作HE染色 ,光镜观察 ,并进行图象分析。结·果·:吗啡依赖组小鼠前列腺和睾丸组织有不同程度萎缩 ;吗啡戒断组小鼠前列腺组织有明显增生 ,睾丸组织有轻度增生 ;吗啡自然戒断后给MT组小鼠前列腺和睾丸组织基本正常。结论··:MT可抑制吗啡戒断小鼠前列腺和睾丸组织的增生。     

清君饮对海洛因依赖大鼠脏器病变的疗效观察

目的 :探讨海洛因依赖大鼠经清君饮治疗后脏器组织结构的恢复情况。方法 :利用电镜对海洛因依赖大鼠用清君饮治疗 2个月后各脏器的病理学改变进行观察。结果 :自然戒断组的心、肝、肺、脑、肾、肾上腺、肌肉组织均有明显的病理变化 ,而清君饮治疗组病变程度较轻。结论 :清君饮治疗后 ,可使病变组织结构尽快地得到恢复     

Changes Produced in the Male Genital Organs of Rabbits and Dogs by 2,6-cis-Diphenylhexamethylcyclo-tetrasiloxane (KABI 1774)

Abstract: The drug. 2,6-cis-diphenylhexamethylcyclotetrasiloxane, was administered daily per os to rabbits (2 mg/kg body weight in soybean oil) for 2, 5, 10, 15, 20, 25, and 30 days, and to dogs (10 mg/kg and 250 mg/kg) for 40 days. Light and electron microscope studies were made on the testis, epididymis and accessory genital glands. In rabbits, cell death was seen in the epididymis, especially in the middle caput after 2, 5 and 10 days. Longer treatment also caused marked atrophy of the epididymal duct epithelium, and some atrophy of the accessory genital glands. After 15 days, spermatozoa no longer showed the morphological maturation changes that normally take place in the caput epididymidis, and the fine structure of the epididymal epithelium suggested a return to prepuberal conditions. After 20 days, spermatozoa in the the cauda epididymidis were dead. The seminiferous tubules showed arrested spermatogenesis followed by degeneration of all spermatids and many spermatocytes between 15 and 25 days. Some ultrastructural changes of the Leydig cell cytoplasm occurred after 10 days, before spermatogenesis was disturbed. In dogs, the effect on the seminiferous epithelium varied from arrested spermatogenesis to complete degeneration of most germ cells. The interstitial cells showed atrophy, shrinkage of the nucleus, and marked loss of the specialized cytoplasmic ultrastructure. The epididymis showed some cell death and very marked epithelial atrophy. The prostate gland showed marked epithelial atrophy, with a few areas also displaying epithelial metaplasia. These observations are compatible with the concept that the cyclotetrasiloxane compound has an antigonadotropic action, but an additional direct antiandrogenic effect on the epididymis may also be involved.     

Insights into testicular damage induced by ethinylestradiol in rats

The present study was conducted to clarify the mechanisms of testicular toxicity induced by ethinylestradiol using a rat model maintaining testicular testosterone levels. Twelve-week-old male SD rats were implanted subcutaneously with testosterone (800 mg)-filled tubes on the back 2 days before ethinylestradiol treatment, and subsequently administered orally 10 mg/kg/day ethinylestradiol for 4 consecutive weeks. At termination, measurements of hormone levels in serum and the testis, sperm head counts in the testis, weights of genital organs and histopathological examination were performed. Results show that the supply of testosterone alone induced markedly increased serum testosterone levels, slightly decreased testicular testosterone levels, and atrophic Leydig cells. Treatment of rats with ethinylestradiol alone significantly decreased testosterone levels in serum and the testis, sperm head counts, and weights in the testis, epididymis and prostate. Histological features included atrophy of Leydig cells, decreased number of elongated spermatids, degeneration of germ cells, and tubular atrophy. Co-administration of testosterone almost completely prevented the aforementioned changes brought about by ethinylestradiol, except for Leydig cell atrophy. From these results, we attribute testicular toxicity during ethinylestradiol exposure to the suppression of testicular testosterone levels.     

Efficacy trial on the purified compounds of the seeds of Carica papaya for male contraception in albino rat

The contraceptive efficacy and toxicological screening of the two principal compounds, MCP I and ECP I, isolated from the seeds of Carica papaya, in male albino rats at the standardized dose regimen, at 50 mg/kg b.w./day, for a period of 360 days and up to 90 days of treatment withdrawal have been reported. The body and organ weights, cauda epididymal sperm characteristics, androgen sensitive tissue biochemistry, reactive oxygen species and anti-oxidant defense system in the cauda epididymal microenvironment, histology and ultrastructure of testis and cauda epididymis, histology of seminal vesicle and prostate, toxicological investigations through routine hematology and serum clinical chemistry, sexual behaviour and fertility index have been studied. The results revealed that oral administration of MCP I and ECP I were equally effective, exhibiting complete inhibition of sperm motility following 90 days of treatment that coincided with a gradual and significant decline in cauda epididymal sperm density, percent viable spermatozoa and significant increase in sperm anomalies. Histology of testis of treated animals revealed degenerated germinal epithelium, vacuolization in Sertoli cells and proliferating germ cells and disturbances in spermatid differentiation. Spermatogonial stem cell reserves and Leydig cells appeared normal. Ultrastructure of the testis revealed vacuolization in the Sertoli cells and germ cells, loss of cytoplasmic characteristics in the Sertoli cells, nuclear degeneration and mitochondrial vacuolization in spermatocytes and spermatids. Leydig cells exhibited steroidogenic features. Cauda epididymis showed normal epithelial cell function. Absence of spermatozoa or disruption of spermatozoa clusters in the lumen were evident. Ultrastructure of cauda epididymis revealed normal secretory activity. Morphology of seminal vesicle and prostate of the treated animals were comparable to control animals. Serum testosterone, tissue biochemical and toxicological parameters remained unaffected. Fertility test revealed 100% efficacy. All the altered parameters showed sign of recovery following 90 days of treatment withdrawal. It is concluded that both MCP I and ECP I are equally effective in terms of contraceptive efficacy which is likely reversible and without adverse side effects.     

Oral administration of Azadirachta indica (L.) seed kernel active principle protects rat liver hepatocytes and testis seminiferous tubules from phenobarbitol-induced damage

The male albino rat testis and liver showed tissue modification upon exposure to phenobarbitol (PB), 24 mg/100 g of body weight, for about 3 weeks and upon staining of their sections with hematoxylin and eosin. In this procedure, the control liver showed normal hepatocytes with centrally placed nuclei, and the PB-treated hepatocyte showed degeneration of cytoplasm and nucleus, necrosis and fragmentation of nucleus, and pushing of nucleus to periphery. The control rat testis showed epithelial layer having broad seminiferous tubules, spermatids, mature spermatozoa, and lumen of seminiferous tubules, and the PB-treated rat testis showed degenerative and necrotic changes in seminiferous tubules and clumping of seminiferous tubules. These changes almost returned to normal conditions in rat liver and testis upon the oral administration of an antioxidant that is present in Azadirachta seed-kernel extract (ASKE, 100 mg/kg body weight). In the case of enzymes, glutathione transferase and glutathione peroxidase were induced upon PB or ASKE treatment and the combination of both the treatments. The lipid peroxides were reduced in all the three cases in both liver and testis. The histological studies and enzymatic analysis revealed that the potential role of ASKE in the protection of the testis and liver tissues from PB-induced damage.     

Sequential analysis of testicular lesions and serum hormone levels in rats treated with a Psoralea corylifolia extract.

In order to clarify pathogenetic targets for the testicular toxicity of a extract of Psoralea corylifolia (P. corylifolia), F344 rats were fed diet containing 3% P. corylifolia extract for up to 12 weeks and subjected to hormone assays and histopathological examination on the testis and epididymis at weeks 1, 2, 4, 8 and 12 (Exp 1). Similar analyses were performed on 1, 3, 7 and 14 days after a single gavage administration of the P. corylifolia extract at a dose of 10 g/kg b.w. (Exp 2). In Exp 1, increase in the numbers of degenerated and exfoliated germ cells and loss of elongated spermatids beyond steps 7 or 8 were initially observed in the seminiferous tubules at week 1, followed by more pronounced degeneration of germ cells with depletion of post-meiotic populations from week 2. The tubular degeneration was associated with Leydig cell atrophy and persistent reduction of serum testosterone and FSH levels throughout the treatment period and a slight reduction of serum LH in later stages. In Exp 2, reduction of serum testosterone and FSH levels preceded degeneration of germ cells in stage VII and VIII tubules at 3 and 7 days after the administration. The results suggest that rapid androgen deprivation reflecting direct interference with Leydig cell function and simultaneous disturbance of the pituitary-testicular axis play pivotal roles in P. corylifolia extract-induced germ cell injury in seminiferous tubules.     

Changes in testicular and serum hormone concentrations in the male rat following treatment with m-dinitrobenzene

m-Dinitrobenzene (m-DNB)-induced testicular atrophy has been attributed to a direct effect upon the germinal epithelium. However, such degenerative changes in the germinal epithelium should induce shifts in the testicular hormonal milieu, which would in turn alter the hypothalamic-pituitary gonadal axis in general. This study evaluated the endocrine status of male rats (killed 3 hr, 24 hr, 1 week, and 2 weeks) following a single oral dose of m-DNB (32 mg m-DNB/kg). Serum and pituitary leuteinizing hormone, follicle-stimulating hormone (FSH), and protactin and hypothalamic gonadotropin-releasing hormone (GnRH) concentrations were determined. Testosterone and androgen-binding protein concentrations in serum, interstitial fluid, seminiferous tubule fluid, and caput epididymis were also determined. In vitro basal and hCG-stimulated testosterone release was determined in the decapsulated testis. Results of the present study indicate that pituitary hormone concentrations and hypothalamic GnRH were unaffected after a single oral dose of m-DNB. Serum FSH was elevated at 2 weeks. There was a transient decrease in serum testosterone at 24 hr, which returned to control values at 1 and 2 weeks. Interstitial fluid, seminiferous tubule fluid, and caput epididymal testosterone concentrations were increased at 1 and 2 weeks. Basal testosterone release in vitro was increased at 2 weeks, while hCG-stimulated testosterone release was increased at 1 and 2 weeks. Androgen-binding protein concentrations in serum and interstitial fluid were increased at 1 and 2 weeks. Androgen-binding protein was increased at 24 hr and 1 week in seminiferous tubule fluid, but returned to control concentrations by 2 weeks. However, the total tubular content of androgen-binding protein was dramatically decreased at 2 weeks. Androgen-binding protein in the caput epididymis was unaltered following m-DNB treatment. These data demonstrate that m-DNB exerts a direct effect on the testes and not through alterations in hypothalamic and pituitary control of gonadal function.     

镉所致大鼠性腺和附性腺的组织病理学改变

【目的】　探讨镉所致大鼠性腺和附性腺的病理学改变。【方法】　各组大鼠分别皮下注射氯化镉 0、0 5、1和 2mg/kg,每天 1次 ,每周 5d ,共 5周。【结果】　染毒大鼠的血镉和尿镉含量显著增高 ,睾丸和附睾体积缩小 ,重量减轻。染毒组睾丸曲细精管壁变薄 ,上皮排列紊乱 ,呈条索状 ,细胞层次明显减少 ;高剂量组曲细精管管腔中无精子 ;附睾上皮细胞呈低柱形 ,排列紊乱 ,管腔中有大量异常精子 ;精囊管壁和前列腺细胞壁稍变薄。【结论】　镉可使染毒大鼠性腺和附性腺重量减轻 ,导致睾丸、附睾出现明显的病理改变。     

Differential distribution of ganglioside GM3 in seminiferous tubule and epididymis of adult rats

Gangliosides are ubiquitous membrane components in mammalian cells and are suggested to play important roles in various functions such as cell-cell interaction, adhesion, cell differentiation, growth control and signaling. Among all ganglio-series gangliosides, GM3 has the simplest carbohydrate structure, and has been shown as a major ganglioside in male reproductive system. To study GM3 distribution in the seminiferous tubule and epididymis, frozen sections were stained with specific monoclonal antibody (MAb) against ganglioside GM3. In the seminiferous tubule of testis, pachytene spermatocytes and spermatids expressed ganglioside GM3, but not in spermatogonia and sertoli cells. Spermatogonia and sertoli cells near the basement membrane were negatively reacted to anti-GM3. In the epididymis, GM3 was expressed only in some interstitial cells. Taken together, these results suggest that the expression of ganglioside GM3 in rat seminiferous tubule and epididymis is spatio-temporally regulated during spermatogenesis.