燃煤型氟中毒对大鼠睾丸超微结构的影响

目的研究燃煤型氟中毒对SD大鼠睾丸超微结构的影响。方法以SD大鼠为研究对象,按体质量均衡随机分为7组:对照组、高氟组、中氟组、低氟组、高氟加营养组、中氟加营养组、低氟加营养组。各染毒组喂饲含不同比例的燃煤型氟中毒病区煤烘玉米的饲料,复制燃煤型氟中毒动物模型。分3批(90 d,120 d,180 d)以股动脉放血法处死动物,查看氟斑牙,测尿氟。常规制作睾丸超薄切片,用透射电镜观察睾丸超微结构的变化。结果 (1)建成氟中毒动物模型,90 d各染毒组均出现氟中毒表现,对照组正常。中毒程度随氟剂量增加和染毒时间延长而加重;氟剂量相同时,营养好,中毒程度轻。(2)对照组结构正常。染毒组曲精小管内各级生精细胞生成减少,精子数量减少,各级生精细胞、睾丸间质细胞、肌样细胞、支持细胞的超微结构均有不同程度的病理变化。随氟剂量增加和染毒时间延长,病变加重。相同染氟剂量和加营养组比较,加营养组病变程度减轻。结论 (1)燃煤型氟中毒对SD大鼠睾丸组织超微结构有明显的损伤作用,随氟剂量和染毒时间延长,病变加重。(2)降低摄氟量及改善营养状况,可改善氟中毒对大鼠睾丸超微结构的损伤。     

燃煤污染型氟中毒大鼠脑组织ERK/p-90RSK信号转导通路研究

目的复制燃煤污染型氟中毒大鼠模型,检测其细胞外信号调节激酶/90ku核小体S6激酶(ERK/p-90RSK)信号通路的变化,探讨燃煤污染型氟中毒中枢神经系统损害的发病机制。方法以贵州省地方性燃煤污染型氟中毒重病区燃煤烘烤的玉米为主要饲料,复制不同摄氟剂量的慢性氟中毒大鼠模型,实验期为6个月。Western-blotting法检测ERK/p-90RSK信号通路相关磷酸化蛋白的表达水平。结果成功建造燃煤污染型氟中毒大鼠模型。检测结果显示,染氟组中大鼠脑组织中p-ERK1/2和p-90RSK蛋白的表达均高于对照组,且高剂量染氟组高于低剂量染氟组,差异有统计学意义(P<0.05)。结论燃煤污染型氟中毒可引起大鼠脑组织中ERK信号转导通路的过度激活,而p-90RSK的激活可能是氟中毒大鼠的反馈性保护机制。     

氧化应激在燃煤污染型氟中毒大鼠中的作用

目的研究氧化应激在燃煤污染型氟中毒大鼠中的作用。方法选择SD大鼠随机分2组（每组11只，雌雄各半），设对照组、染氟组。染氟组以氟中毒病区煤烘玉米为主要饲料，复制氟中毒动物模型，检查氟斑牙、尿氟浓度及血清、肝、肾、脑组织中丙二醛（MDA）含量、超氧化物歧化酶（SOD）及谷胱甘肽还原酶（GR）活性，及血清中反映肝、肾功能的指标。结果染氟组大鼠血清、肝、肾、脑组织中MDA含量升高，SOD和GR活性明显降低（P〈0．05或P〈0．01）。同时大鼠肝、肾功能已有一定的改变。结论氟中毒大鼠机体内氧化系统与抗氧化系统失衡，氧化应激引起的氧化损伤作用在氟致大鼠肝、肾毒性中起着重要的作用。     

燃煤型氟中毒儿童及成人血锌含量调查

目的：调查分析燃煤型氟中毒儿童与成人血锌含量的改变状况。方法随机选取本市燃煤型氟中毒患者50例和当地健康人群50例作为观察对象,以燃煤型氟中毒患者为研究组,以健康人群为对照组。给予两组进行空腹抽取静脉血,同时测定血锌的含量,此外,收集尿液及测尿氟的含量,然后组间比较差异。结果研究组中尿氟含量相对于对照组比较高（P〈0.05）,血锌含量相对于对照组比较低（P〈0.05）。结论在燃煤型氟中毒的儿童及成人中,其体内的血锌含量出现降低的现象。     

小柴胡汤对大鼠慢性氟中毒致肝损伤的保护作用

目的:观察小柴胡汤对大鼠慢性氟中毒致肝损伤的治疗作用,探讨小柴胡汤在对抗氧化应激中的保护作用,为氟中毒的防治提供理论依据.方法:将SD大鼠随机分为空白对照组、模型组、小柴胡汤实验组和小柴胡汤阴性对照组.以NaF溶液(100 mg/L)为氟源,建立慢性氟中毒大鼠模型.小柴胡汤实验组、小柴胡汤阴性对照组大鼠给予小柴胡汤中药...     

正常大鼠血清微量睾酮的检测及实验性影响因素

目的:为了检测大鼠血液中微量睾酮的含量,研究正常大鼠血清睾酮水平的变化规律及实验性影响因素.方法:应用全自动微粒子化学发光免疫分析系统(BECKMAN COULTER AccessImmunoassay System)及配套的睾酮试剂盒测定正常大鼠的血清睾酮含量.结果:(1)430只正常大鼠的血清睾酮含量为(4.64±2.48)ng/mL.(2)不同采血方式在相同时间点采血测定的大鼠血清睾酮含量存在差异.(3)以玻璃毛细管球后静脉丛间隔4h连续多次采血可使大鼠的血清睾酮水平明显下降,以8h下降最为明显.(4)24h内大鼠的血清睾酮含量存在昼夜节律,8:30的血清睾酮含量明显高于20:30.结论:正常大鼠的血清睾酮水平差异较大,分布范围较宽.不同采血方式、不同采血时间及反复多次采血对大鼠血清睾酮含量的影响较大.上述因素可能是激素测定数据波动较大的主要原因.本实验结果为选择合适的采血方式及适当的采血时间提供参考.     

燃煤型地氟病的流行及其预防

地方性氟中毒是指人在特定的地理环境中摄入过量的氟而导致的全身慢性蓄积中毒.它是世界上也是我国分布最为广泛、危害最为严重的一种地方病,在全球五大洲的40多个国家都有流行.我国为地氟病大国,除上海外各省、市、自治区均有流行.地方性氟中毒根据氟源和人体摄氟的不同途径,大体上可分为饮水型、燃煤污染型、饮茶型和混合型四种.其中,燃煤污染型地方性氟中毒,是上世纪70年代后期被确认的,我国独有的一种病区类型[1].     

硒、钼、硼对氟中毒大鼠氟斑牙发生的影响

目的 研究硒、钼、硼对氟中毒大鼠的氟斑牙发生的影响.方法 Wristar大鼠随机分为8组(雌雄各半):硒1组、硒2组、钼1组、钼2组、硼1组、硼2组、氟组、对照组.各组均喂以舍F-45mg/L的蒸馏水及舍不同浓度微量元素的饲料,观察大鼠的一般情况,氟斑牙的发生.结果 硒组体质量增加与对照组接近,优于钼组和硼组(P＜0....     

清镇市流长乡燃煤污染型氟中毒流行现况及儿童免疫功能初探

贵州省是生活燃煤污染型氟中毒的重病区。研究表明,过量氟主要对骨骼等硬组织造成损伤、也损害非骨相系统,如神经系统、内分泌系统、心血管系统肝、肾等,但氟化物对儿童免疫系统的损害研究报道较少。本研究通过流行病学,细胞免疫和体液免疫功能研究,了解燃煤型地方性氟中毒对儿童     

蛋白质摄入量对慢性氟中毒大鼠骨病变的影响——形态计量学研究

本文用形态计量学方法结合血清 F~-、骨氟含量测定研究了高(32%)、中(21%)、低(12%)蛋白质摄入对慢性低超常量氟中毒大鼠骨病变的影响。结果表明:1.饮用5ppm F~-的高氟水12个月可以诱发大鼠高氟血症和氟中毒。2.大鼠的骨氟蓄积量有随蛋白质摄入量减少而增加的趋势。3.只在低蛋白质摄入的氟中毒大鼠中诱发了有意义的骨病变。这说明低蛋白摄入会促进氟骨症的发生,高蛋白摄入则有可能减缓氟骨症的发生或减轻其严重程度。由于本实验诱发大鼠氟中毒的条件与国内一些高氟区人群饮水含氟量相近,故本文结果提示:对高氟区人群的蛋白质营养状况应予以关注。     

EFFECTS OF ETHANE DIMETHANESULFONATE ON THE STRUCTURE OF ADULT MALE RAT ADRENAL CORTEX

The influence of ethane dimethanesulfonate (EDS), a specific toxicant for Leydig cells, on the morphometric characteristic of adult male rat adrenal cortex was examined on day 15 after administration. As expected, the dose of 75 mg kg⁻¹of EDS produced drastic reduction in serum testosterone levels followed by a decrease in testis and seminal vesicle weight. However, a considerable drop (over 50%) in adrenal weight was also found. Stereological analysis of the adrenal cortex, performed under light microscope, revealed atrophy of all adrenocortical zones. The changes were most prominent in the inner zones. Thus, in the zona fasciculata the number of parenchymal cells was markedly decreased. In the zona reticularis a layer consisting mostly of atrophic parenchymal cells was localised at the border between zona reticularis and zona fasciculata. The remaining small number of cortical cells in this zone displayed a notable hypertrophy. It is concluded that EDS at a dose that destroys Leydig cells has a strong deleterious effect on steroidogenic cells of adult male rat adrenal cortex.     

Effects of acute administration of ethanol on the rat adrenal cortex

OBJECTIVE: The purpose of this study was to investigate the effect of a single dose of ethanol on rat adrenal cortex and to determine whether the estrous cycle can influence this effect of ethanol. METHOD: Adult female Wistar rats showing proestrus or diestrus Day 1 (n = 12) were treated intraperitoneally with ethanol (4 g/kg body weight). Untreated (n = 15) and saline-injected (n = 14) rats were used as controls. The animals were sacrificed by decapitation 0.5 hour after ethanol administration. Stereological analysis was performed on paraffin sections of adrenal glands stained with AZAN, and the following parameters were determined: absolute volume of the zona glomerulosa, the zona fasciculata and the zona reticularis, numerical density, volume and the mean diameter of adrenocortical cells and of their nuclei, and diameter and length of capillaries. RESULTS: The diameter and volume of adrenocortical cells in the zona fasciculata and the zona reticularis were significantly increased by acute ethanol treatment at proestrus. In the same group of animals, a single dose of ethanol induced significant decrease in numerical density of adrenocortical cells and of their nuclei in all three zones. Increased length of capillaries of the zona fasciculata as well as enhanced level of serum corticosterone was found in ethanol-treated rats at both phases of the estrous cycle, proestrus and diestrus Day 1. CONCLUSIONS: The obtained results indicate that a single dose of ethanol activates adrenal cortex in female rats and that the effect is more pronounced on morphometric parameters at proestrus.     

Effect of atenolol on cadmium-induced testicular toxicity in male rats

Cadmium-induced stress adversely affects testicular activity and causes sympathetic stimulation. To investigate the effect of atenolol, a β-adrenergic receptor blocker, on testicular androgen synthesis after cadmium treatment, adult Sprague-Dawley strain male rats were given a single sc dose of cadmium chloride 0.45 mg/kg BW. Animals were killed on day 3 after treatment. Adrenal weight, adrenal Δ⁵-3β-hydroxysteroid dehydrogenase (Δ⁵-3β-HSD) activity, serum corticosterone, and brain noradrenaline were increased significantly while testicular Δ⁵-3β-HSD and 17β-HSD activities, serum testosterone, and accessory sex organs weight were decreased. Oral coadministration of atenolol at a dose of 2.0 mg/kg body weight for 3 days resulted in complete protection of adrenal Δ⁵-3β-HSD, testicular Δ⁵-3β-HSD, and 17β-HSD activities, adrenal weight, serum corticosterone, and serum testosterone when compared with cadmium-only group and there were no significant differences in these parameters from the vehicle control values. Simultaneous administration of cadmium and atenolol also protected brain noradrenaline content and reduced the rise of testicular cadmium concentration. All the parameters were similar to control levels in rats treated with atenolol alone. We conclude that atenolol may protect testicular androgen synthesis by inhibiting the action of noradrenaline on testicular Leydig cells and adrenocortical hyperactivity in cadmium-treated rats.     

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.     

Cimetidine-induced Leydig cell apoptosis and reduced EG-VEGF (PK-1) immunoexpression in rats: Evidence for the testicular vasculature atrophy

The antiulcer drug cimetidine has shown to cause changes in the testicular microvasculature of adult rats. Since Leydig cells (LCs) produce the pro-angiogenic factor, EG-VEGF (endocrine gland-derived vascular endothelial growth factor), also known as prokineticin 1 (PK-1), this study examined the effect that cimetidine might have on LCs in testes with damaged vasculature. Rats received intraperitoneal injections of 100 mg/kg of cimetidine (cimetidine group) or saline vehicle (control group) for 50 days. Serum testosterone levels were measured by chemiluminescence immunoassay and testicular sections were subjected to TUNEL and immunohistochemical reactions for caspase-3, 17β-HSD6, CD163 (ED2 macrophage), PK-1 and androgen receptor (AR). LCs in the cimetidine group showed TUNEL and caspase-3 positive labeling and apoptotic ultrastructural features. Moreover, the presence of 17β-HSD6-positive inclusions inside macrophages and the reduced number of LCs, AR immunoreactivity and serum testosterone levels correlated with a decrease in either the number of PK-1-immunostained LCs or PK-1 immunoreactivity. Although it is not clear which cell type is the primary target of cimetidine in the testicular interstitial compartment, these findings support a direct link between cimetidine-induced testicular vascular atrophy and LCs damage.     

Study of the effects of aging on macromolecular synthesis in mouse steroid secreting cells using microscopic radioautography

The effects of aging on DNA, RNA and protein synthesis in adrenal gland cortical cells and testicular Leydig cells of ddY mice at various ages (from prenatal day 19 to postnatal days 1, 3, 7, 14, months 1 and 6 and 1 and 2 years after birth) were examined using light and electron microscopic (EM) radioautography after labeling with [3H]-thymidine, [3H]-uridine and [3H]-leucine. The percentage of the labeled cells in the adrenal glands after [3H]-thymidine injection was greatest in the zona glomerulosa of the cortex and the medulla on embryonic day 19, in the zona fasciculata and zona reticularis of the cortex on postnatal day 1 and gradually decreased with aging. EM radioautography revealed that well developed cell organelles such as smooth surfaced endoplasmic reticulum, Golgi apparatus, mitochondria with tubular cristae and lipid droplets were more frequently observed in the cytoplasm of unlabeled cells as compared to cells labeled with [3H]-thymidine in the three zones of the cortex. The effects of aging on RNA synthesis in adrenal glands after [3H]-uridine injection revealed that all types of cells of the adrenal gland were labeled. In each cell, silver grains were localized over the nuclei and cytoplasm and were more dense in the nuclei than the cytoplasm. Grain counts were highest in the cortex and medulla on fetal day 19 and then gradually decreased with aging from postnatal day 14 to 1 year after birth. In the cortex, the number of silver grains was higher in the zona glomerulosa than in the other zones from fetal day 19 to 1 year and grain counts were higher in the medulla in the embryonic stage as compared to the postnatal stages. However, the number of labeled mitochondria and the mitochondrial labeling index increased with aging. The [3H]-thymidine labeling index in the Leydig cells of the testis was low at embryonic and early postnatal stages, increased slightly at 6 months and reached a peak at 9 months which was maintained at a relatively high level in senescence. The number of the silver grains over the nuclei and cytoplasm of Leydig cells due to [3H]-uridine labeling was observed from embryonic day 19 and increased from month 3 onwards. From adult to senescence, [3H]-uridine incorporation was maintained at high levels in the nuclei and was relatively low in the cytoplasm. The effects of aging on [3H]-leucine incorporation in Leydig cells were also examined. The labeling indices between embryonic and early postnatal stages showed no obvious differences although the number of the silver grains in both cytoplasm and nucleus increased from 6 months onwards and was maintained at high levels until senescence. From these results, it was concluded that the effects of aging on DNA, RNA and protein synthesis in steroid secreting cells such as adrenal gland cortical cells and testicular Leydig cells of mice correlated with the hormonal changes observed with aging.     

Testicular effects of the Leydig cell toxicant ethane dimethanesulphonate given to neonatal rats.

Neonatal rats were injected with either 50 mg/kg ethane dimethanesulphonate (EDS) or vehicle on days 1 to 5 inclusive or on day 1 alone. Studies were made on days 6, 28, and 63 of testicular structure; related endocrinologic parameters were measured in the day 1 to 5 treated animals only. Leydig cells and their activities were identified by cell counts using sections stained for 3 beta-hydroxysteroid dehydrogenase, hCG binding to LH receptors in testicular homogenates, and assays of intratesticular testosterone, plus pituitary and/or serum concentrations of testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH). Given on days 1 to 5, EDS reduced Leydig cell populations estimated by morphometry and 125I-HCG binding, and testicular and body weights between days 6 and 63, and permanently retarded the development of the seminiferous epithelium. Decreases of serum and intratesticular testosterone occurred with homeostatic rises in FSH and LH. Injection on day 1 reduced Leydig cell numbers only on day 6 although body weight remained retarded. The data illustrate the susceptibility of the developing rat testis to the cytotoxicant EDS; whether this is related to withdrawal of androgen production or nonspecific cytotoxicity remains to be evaluated.     

Effects of excess corticosterone on NADPH generating enzymes and glucose oxidation in Leydig cells of adult rats

Clinical and experimental studies have shown the adverse effects of excess glucocorticoid on testicular testosterone production. The NADPH co-enzyme has been recognized as an important factor that regulates several steps in steroidogenesis, while glucose oxidation acts as a limiting factor on testicular testosterone production. Nevertheless, the impact of excess corticosterone, the stress hormone on testicular NADPH availability and glucose oxidation is unknown. Therefore, the present study was designed to assess the specific effects of excess corticosterone on Leydig cell NADPH generating enzymes and glucose oxidation. Adult Wistar rats (200-250 g, b.w.) were treated with corticosterone-21-acetate (2 mg/ 100 g, b.w., i.m., twice daily) for 10 days and corticosterone-21-acetate plus luteinizing hormone (LH) (100 microg/kg b.w., i.m., daily) for 10 days. After the treatment period, experimental animals and controls were killed, blood was collected and the sera separated for testosterone assay. Testes were removed and Leydig cells were isolated, purified and used for estimating the specific activity of NADPH generating enzymes and 14C-glucose oxidation. Serum testosterone, Leydig cellular 14C-glucose oxidation and the specific activities of 6-phosphogluconate dehydrogenase (6-PGDH), NADP-isocitrate dehydrogenase (ICDH) and malic enzyme were significantly decreased in corticosterone-treated rats. Co-administration of LH with corticosterone maintained the specific activities of 6-PGDH and ICDH and 14C-glucose oxidation at control level. Nevertheless, serum testosterone and Leydig cellular malic enzyme activity showed a significant decrease in these rats. In conclusion, the inhibitory effects of excess corticosterone on Leydig cell steroidogenesis are mediated through impaired glucose oxidation and defective NADPH generation. Co-administration of LH with corticosterone failed to prevent the decrease in serum testosterone and Leydig cell malic enzyme activity, suggesting the dominant inhibitory effects of excess corticosterone.     

Effect of oral administration of terephthalic acid on testicular functions of rats

To investigate the toxic effect of terephthalic acid (TPA) on testicular functions of rats, male Sprague-Dawley rats were orally administered TPA in diet at the levels 0 (control), 0.2, 1 and 5% for 90 days. Testicular functions were assessed by histopathology, testicular sperm head counts, daily sperm production, sperm motility (measured by computer-assisted sperm analysis, CASA), biochemical indices (marker testicular enzymes), and serum testosterone. Oral feeding with terephthalic acid did not cause body and testes weight loss in TPA-treated groups. Histopathologically, damages of spermatogenic cells and Sertoli cells were observed by electron microscope, testicular sperm head counts, daily sperm production, and activities of sorbitol dehydrogenase (SDH) were decreased significantly in the 5% TPA group. The motility of spermatozoa was reduced significantly in all treated groups, which was correlated with administration doses. Serum testosterone concentrations were not declined in treated groups. In conclusion, TPA can cause impairment of testicular functions. The primary sites of action may be spermatogenic cells and Sertoli cells. The results of the present study provide first information of TPA on testicular functions in male rats.