纳米二氧化钛对雄性小鼠生殖系统的影响

目的:研究纳米二氧化钛(TiO2)对雄性小鼠的在体作用,主要观察其对雄性小鼠生殖系统的影响。方法:45只6周龄的雄性ICR小鼠随机均分3组,实验组隔日腹腔注射纳米TiO2(200mg/kg或500mg/kg),对照组注射等体积生理盐水,共给药5次。停药1周后,测量心脏、肝、肾、脾、睾丸和附睾的脏器系数,血清生化指标、睾酮和雌二醇水平;显微镜下观察附睾精子数量、活率、畸形率和睾丸内精子计数;主要脏器作病理切片和HE染色,TUNEL法检测睾丸生殖细胞凋亡。结果:与对照组相比,给药200mg/kg纳米TiO2组上述指标均无明显改变(P>0.05);给药500mg/kg组小鼠的心、肝和肾质量系数显著降低(P<0.05);丙氨酸氨基转移酶(ALT)、丙氨酸氨基转移酶/天门冬氨酸氨基转移酶(ALT/AST)、尿素氮(BUN)均显著升高(P均<0.05);附睾精子数、精子活率以及睾丸内精子计数均显著降低,精子畸形率增高,睾丸生殖细胞凋亡明显增多(P均<0.05)。肝、肾、脾、睾丸和附睾的病理切片观察未见明显改变。结论:小剂量的纳米TiO2对雄性小鼠无明显影响,较大剂量的纳米TiO2对雄性小鼠肝、肾功能有轻度影响,对小鼠精子生成和精子功能有明显影响,并诱导睾丸生殖细胞凋亡。     

吸烟对大鼠生精细胞发育影响的研究

目的:探讨吸烟对大鼠生精细胞发育的影响。方法:自制吸烟机将大鼠制成被动吸烟模型,大鼠随机分成被动吸烟组(A、B组各10只)及相应对照组(C、D组各10只),A、B组被动吸烟8周,随后处死A组及相应对照组C组大鼠;B组停止被动吸烟后与其相应对照组D组继续观察48 d后处死。流式细胞术(FCM)检测各组大鼠生精细胞周期,放免法测定血睾酮(T)、黄体生成素(LH)水平,HE染色观察睾丸组织结构变化,透射电镜观察睾丸超微结构改变。结果:与C组比较,A组大鼠精子、精子细胞[(18.76±3.58)%]和初级精母细胞[(5.71±1.18)%]明显减少(P均<0.01),而精原细胞[(55.98±5.35)%]增加(P<0.01),增殖指数降低(P<0.01)。A组大鼠生精小管壁变薄,层次减少,生精小管内精原细胞减少,精母细胞固缩。间质细胞内质网扩张脱颗粒,高尔基复合体减少,支持细胞脂滴和溶酶体增多。A组大鼠T、LH水平低于C组(P均<0.01)。B组大鼠停止被动吸烟后,精子、精子细胞、初级精母细胞比例和增殖指数上升,T、LH水平升高,但仍低于D组。结论:吸烟导致大鼠睾丸生精上皮损伤及间质细胞和支持细胞受损,同时伴有T和LH水平的下降,延缓生精细胞增殖,停止吸烟后生精功能有逐渐恢复的趋势。     

醋酸甲孕酮对雄性大鼠骨髓嗜多染红细胞和生精细胞微核的影响

背景与目的:观察单独使用不同剂量的醋酸甲孕酮(Meddroxy progesterone acetate,MPA)对雄性大鼠骨髓和生精细胞微核的影响.材料与方法:50只大鼠分组后,给予每月一次MPA(37.5或75或150 mg/kg)肌肉注射;另以等体积生理盐水为对照,共3个月,每组中的一半动物在停药后即处死,另一半动物在停药9个月后处死.测定各组大鼠给药后骨髓与生精细胞微核率和精子计数及形态.结果:与对照组相比,各实验组大鼠生精功能均明显受到抑制.各实验组大鼠骨髓嗜多染红细胞的微核发生率无明显升高.各实验组生精细胞微核率明显增加,同时附睾精子观察不仅精子数量下降,而且畸形率升高,其中大剂量MPA组生精细胞微核率增加和精子畸形率升高最为明显;但停药9个月后各实验组生精细胞微核率下降至空白对照水平,同时附睾精子数量增加,畸形率减低.结论:单独使用MPA对雄性大鼠体细胞无致突变效应;虽然可以引起生精细胞微核率明显增加,但停药9个月后恢复.     

芹菜素对雄性小鼠肝脏功能影响的实验研究

目的观察不同剂量、不同作用时间,芹菜素(Apigenin)对雄性小鼠肝脏生化指标的影响,探讨其剂量和时间效应,为芹菜素的深入研究和开发利用提供科学依据。方法将200只健康SPF级昆明种雄性小鼠按体质量随机分为4组,分别为阴性对照组(生理盐水10 mL/kgbw)、低剂量组(AP 252 mg/kgbw)、中剂量组(AP504 mg/kgbw)和高剂量组(AP 1 008 mg/kgbw),每组50只。每天灌胃1次,连续7、14、21、28和35 d后,内眦静脉丛取血,检测血清总蛋白(TP)、白蛋白(ALB)、球蛋白(GLO)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、谷氨酰转肽酶(GGT)和碱性磷酸酶(ALP)活力。结果 7 d高剂量组TP、ALT、ALB、AST、ALP与相应对照组比较升高,差异有统计学意义(P<0.05);14 d中剂量组TP、ALB、ALT、AST与相应对照组比较升高,差异有统计学意义(P<0.05);21 d低剂量组TP、ALB、ALT、AST与相应对照组比较升高,差异有统计学意义(P<0.05);35 d ALB、ALT、AST、ALP低剂量组、中剂量组、高剂量组与对照组比较降低,差异有统计学意义(P<0.05)。结论该实验条件下,芹菜素影响了雄性小鼠肝脏功能;芹菜素灌胃1 008 mg/kgbw 7 d、504mg/kgbw 14 d、252 mg/kgbw 21 d可能是雄性小鼠肝脏血液生化指标变化的敏感时期。     

母代高脂饮食诱导子代在小鼠生命早期出现糖脂代谢紊乱且具有雄性易感性

目的 探讨孕期和哺乳期的高脂饮食能否导致子代在生命早期出现糖脂代谢紊乱。方法 成年雌性C57BL/6J小鼠与正常饮食雄性小鼠进行交配,孕鼠随机分为高脂饮食组和正常饮食组,在孕期和哺乳期喂养高脂饲料或正常饲料,至交配后第一代鼠断乳时（3周龄）观察其糖脂代谢相关性指标以及肝脏病理表现。结果 较正常饮食组子鼠相比,高脂饮食子鼠出生体重更低（P<0.05）。在断乳时,高脂饮食组雄性子鼠体重较重（P =0.038）,腹腔糖耐量实验 30 min和60 min血糖明显升高（P值分别为<0.001和<0.01）,糖耐量曲线下面积较大（P=0.0016）,HOMA-IR值较大（P<0.05）,雌性子鼠腹腔糖耐量实验在30 min血糖高于正常组（P<0.01）,而糖耐量曲线下面积和HOMA-IR值在两组之间无明显统计学意义。雄性和雌性子代小鼠空腹胆固醇水平高脂饮食组均高于正常饮食组（P值分别为<0.0001和0.0004）,而两组雄性和雌性子代小鼠空腹胰岛素和甘油三酯水平差异均无显著性（P 均>0.05）。另外,在断乳时高脂饮食子鼠出现肝脏脂肪变性,雌性和雄性子鼠无明显差异。结论 母鼠孕期和哺乳期高脂饮食能够诱导子代在生命早期就能出现糖脂代谢紊乱并且雄性子鼠更易出现肥胖、糖耐量异常、胰岛素抵抗。     

Intermittent hypoxia with or without hypercapnia is associated with tumorigenesis by decreasing the expression of brain derived neurotrophic factor and miR-34a in rats

Background Very recent studies revealed that obstructive sleep apnoea （OSA） is a contributor of the increased incidence and mortality of cancer in humans,but mechanisms of how OSA promotes tumorigenesis remains largely unknown.We investigated whether intermittent hypoxia with and without hypercapnia plays a role in tumorigenesis.Methods First,Sprague-Dawley （SD） male rats （12 weeks old） were subjected to different hypoxia exposures：intermittent hypoxia and intermittent hypoxia with hypercapnia; continuous hypoxia and normal air.The systemic application of chronic fast rate hypoxia with or without hypercapnia mimicked severe OSA patients with apnoea/hypopnea index equivalent to 60 events per hour.Then routine blood tests were performed and the levels of brain derived neurotrophic factor （BDNF） and miR-34a were examined.Results In contrast to intermittent hypoxia with hypercapnia,both intermittent hypoxia and continuous hypoxia treatments caused significantly higher levels of haematology parameters than normoxia treatments.Compared to normoxia,intermittent hypoxia with hypercapnia exposure resulted in substantial decrease of serum BDNF and,miR-34a in the lower brainstem,while less pronounced results were found in intermittent hypoxia and continuous hypoxia exposure.Conclusions The exposure of intermittent hypoxia with or without hypercapnia,mimicking the situations in severe OSA patients,was associated with,or even promoted tumorigenesis.     

Endocrine Disruption of Cadmium in Rats Using the OECD Enhanced TG 407 Test System

Objective To evaluate the endocrine disrupting effects of cadmium(Cd) using OECD enhanced TG407 test guideline. Methods Sprague-Dawley(SD) rats were randomly divided into six groups and accordingly administered with 0, 1, 2.5, 5, 10, 20 mg/kg·BW/day of Cd by gavage for 28 days. Body weight, food consumption, hematology, biochemistry, sex hormone levels, urinary β2-microglobulin, organ weights and histopathology and estrous cycle were detected. Results Cd could significantly decrease animals' body weight(P0.05). Serum luteinizing hormone(LH) at 10-20 mg/kg·BW groups and testosterone(T) at 2.5 and 10 mg/kg·BW groups decreased significantly(P0.05). However, no statistically significant change was found in urinary β2-microglobulin among Cd-treatment groups(P0.05). Endpoints related to female reproduction including uterus weight and histopathological change at 10-20 mg/kg·BW groups showed significant increase(P0.05). While among male rats in 2.5, 10, 20 mg/kg·BW groups, weight of prostate, thyroids, and seminal vesicle glands significantly decreased(P0.05). Moreover, no histopathological change was observed in kidney. Conclusion Results suggested that Cd can cause endocrine disrupting effects in SD rats. Comparing with possible renal toxicity of Cd, its toxicity on endocrine system was more sensitive.     

除草剂阿特拉津对雄性动物生殖功能的影响

阿特拉津(ATR)是一种在世界范围内得到广泛应用的除草剂,由于长期大量的使用,目前ATR在环境中已经广泛分布,其对环境和人类健康的威胁逐渐成为人们关注的焦点.已有的研究表明,ATR对生物体具有一定的生殖和发育毒性.本文将从精子的形态、生殖激素、性分化和生殖器官的发育四个方面,针对阿特拉津对雄性动物生殖功能的影响进行综述,介绍近年来国内外取得的研究进展.     

Expression of Attractin in male reproductive tract of human and mice and its correlation with male reproduction

The expression of Attractin mRNA and protein in testis and semen of human and male mice was investigated. Human testis and semen samples were all collected from Reproductive Center of Reumin Hospital, Wuhan University in December, 2012. Testis samples were collected from 7 cases of obstructive azoospermias when they were subjected to diagnosed testis biopsy, and 30 nor- mal human semen samples were obtained from those cases of semen analysis. Adult mice testis tis- sues were obtained from 10 2-month-old male BALB/c mice, and 60 male mice at different ages were classified into 10 groups （day 1, 5, 10, 15, 21, 28, 35, 42, 56, and 120 respectively, n=6 each）. The expression of Attractin mRNA and protein in testis was detected by RT-PCR and Western blotting re- spectively. Human semen samples were centrifuged into sperm plasma （SP） and sperm extract （SE）, and mice sperm samples were collected from the epididymis of 10 adult male BALB/c mice. Western blotting was used to determine the Attractin protein expression level. Attractin mRNA and protein were expressed in the testis of both patients with obstructive azoospermias and adult Bcl/B mice. Quantitative RT-PCR revealed that no Attractin mRNA was detectable in day 1 male BALB/c mice group. The Attractin mRNA and protein levels were low on the day 10, and increased with age until day 56. On the day 120, the expression levels of Attractin were decreased. As for human semen sam- pies, Attractin protein was expressed in both SP and SE, but didn＇t exist in samples from the epidi- dymis of male BALB/c mice. It was suggested that Attractin acted as a novel active substance and was involved in male reproduction in both human and BALB/c mice, but it exerted a different ex- pression profile in different mammal species.     

十一酸睾酮对雄性家兔髂动脉内膜损伤后的修复作用

目的观察十一酸睾酮对雄兔髂动脉内膜损伤后的修复作用。方法成熟雄性日本大耳白兔25只,随机分成5组,每组5只:假手术组(不切除睾丸和附睾)、模型组、小剂量组(手术后补充睾酮3mg/kg)、中剂量组(手术后补充睾酮6mg/kg)和大剂量组(手术后补充睾酮12mg/kg),后4组均切除双侧睾丸和附睾。所有动物手术后第14d行右侧髂动脉内皮剥脱术。手术后第7、14和第21d肌肉注射十一酸睾酮,假手术组和模型组肌注生理盐水。于不同时间测定血清总睾酮。第28d处死动物,取损伤血管段,应用扫描电镜和HE染色观察髂动脉内膜的修复情况。结果光镜下观察发现,模型组、小剂量组和中剂量组动脉内膜增生严重,大剂量组内膜增厚程度明显减低,接近假手术组。模型组、小剂量组和中剂量组的髂动脉内膜/中膜面积比值分别是1.25±0.10、0.90±0.10和0.74±0.11,明显高于假手术组(0.22±0.05;P<0.01)。大剂量组的髂动脉内膜/中膜面积比值为0.26±0.07,接近于假手术组(P>0.05)。扫描电镜观察发现,假手术组动物髂动脉内皮光滑,整齐连续,模型组几乎未见到有内皮细胞再生,小剂量组内皮有散在覆盖,中剂量组片状覆盖,大剂量组内皮细胞修复明显,排列趋于正常,偶有缺失。在手术后第28d大剂量组血清总睾酮水平接近假手术组,其它组在不同时间点均低于假手术组。结论生理水平的睾酮具有保护雄性家兔血管内皮,抑制动脉损伤后内膜增生的作用。