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。     

齐墩果酸脂质体对顺铂所致小鼠少弱精子症的保护作用研究

目的:研究齐墩果酸脂质体(OA-Lips)对顺铂所致小鼠少弱精子症的保护作用。方法:将60只ICR小鼠随机分为对照组,模型组,阳性对照组,OA-Lips低、中、高剂量组,每组各10只。OA-Lips低、中、高剂量组每天分别给予25、50和100 mg/kg OA-Lips水溶液灌胃,阳性对照组每天给予50 mg/kg维生素E水溶液灌胃。第28天,除对照组外,其余各组小鼠均给予1次10 mg/kg顺铂溶液腹腔注射,对照组小鼠则给予相同剂量生理盐水腹腔注射。给药3 d后处死小鼠并取材,检测小鼠精子浓度和运动学参数、睾丸组织经HE染色检测,酶联免疫试剂盒测定睾酮水平。结果:与模型组相比,OA-Lips高剂量组活动精子百分率以及精子浓度显著升高(P<0.05)。睾丸组织经HE染色后,相较于模型组,OA-Lips可以显著改善睾丸组织的损伤(P<0.05),对生精小管和间质细胞有一定的保护作用。随着OA-Lips的使用剂量增加,各组小鼠前向运动的精子数量逐渐升高,各剂量组小鼠精子的VCL、VSL、VAP、LIN、STR、WOB、ALH和BCF逐渐升高。OA-Lips各剂量组小鼠血清中睾...     

不同剂量的十一酸睾酮对大鼠生精功能影响

目的 :进一步了解睾丸内睾酮和生精功能的关系。　方法 :大鼠给予不同剂量的十一酸睾酮 (TU)后测定大鼠血清、睾丸间质液和睾网液内睾酮水平 ,以及附睾精子的数量、活力 ,以观察二者之间关系。结果 :大鼠给予不同剂量的十一酸睾酮后 ,睾丸内睾酮水平发生不同的变化 ,随之睾丸内生精功能也发生变化。低剂量十一酸睾酮(8mg/kg)不影响睾丸内睾酮水平 ,也不影响睾丸内的生精过程。附睾精子的数量、活动力与对照组无显著性差异。但给予超生理剂量 (30mg/kg) ,则抑制睾丸内睾酮的产生 ,睾丸内睾酮水平显著下降 ,使精子的发生明显受到抑制。而给予超大剂量的外源性睾酮 (6 2 5mg/kg) ,尽管抑制了睾丸内睾酮的产生 ,但由于补充了大量外源性睾酮 ,使睾丸内睾酮维持在正常水平。精子的发生能维持在正常水平。附睾精子的数量与活动力与对照组无显著性差异。　结论 :进一步论证了睾丸内高浓度的睾酮对维持生精过程起到决定性的作用     

大豆黄酮对雄性大鼠生殖器官生长发育的影响

目的:探讨植物雌激素大豆黄酮对大鼠睾丸和附睾生长、发育的影响。方法:10周龄(成年早期)和4周龄(青春期)SD雄性大鼠各30只,分别分为5组:正常对照组,阳性对照组、低、中、高剂量大豆黄酮组,6只/组,分别给予生理盐水、0.1mg/kg己烯雌酚,2、20、100mg/kg大豆黄酮灌胃,连续90d,观察睾丸、附睾指数及体重的变化;HE染色观察睾丸、附睾等组织结构的改变。结果:在成年早期大鼠中,各剂量大豆黄酮组大鼠的体重、睾丸和附睾指数与正常对照组均无显著差异(P均>0.05);在青春期大鼠中,各剂量大豆黄酮组大鼠的附睾指数与正常对照组亦无显著差异(P均>0.05);而高剂量组大鼠的睾丸指数(3.21±0.07)显著低于正常对照组(3.71±0.32,P<0.05),中、低剂量组与正常对照组差异无显著性(P均>0.05);中、低剂量组大鼠的体重与正常对照组无显著性差异(P均>0.05),而高剂量组的体重则显著低于正常对照组(P<0.05)。HE染色结果显示青春期及成年早期大鼠摄入各剂量大豆黄酮对附睾组织结构无明显影响,而摄入高剂量大豆黄酮可使青春期大鼠睾丸发育迟缓,出现不同程度生精障碍。结论:青春期摄入高剂量的大豆黄酮对SD大鼠睾丸生长发育及组织结构有一定影响。     

氰戊菊酯对雄性大鼠生殖内分泌系统的影响

目的 :研究氰戊菊酯 (Fen)对雄性生殖内分泌系统的损害作用及其机制。　方法 :将不同剂量的Fen(0、2 .4、12、6 0mg/kg) ,每日分别对雄性成年SD大鼠连续灌胃 ,染毒 15、30d ,应用RIA法测定大鼠血清中FSH、LH、T和睾丸匀浆中T的水平 ,同步测定睾丸标志酶ACP、γ GT的活性 ,并采用精子头计数法观测每日精子生成量 (Spr)的变化。　结果 :与对照组相比 ,染毒 15d时 ,血清中FSH水平在≤ 12mg/kg剂量组均明显升高 (P <0 .0 1) ,血清中LH含量在 12mg/kg剂量组显著增加 (P <0 .0 1) ,而睾丸匀浆中T在≥ 12mg/kg剂量组中表现为显著下降 (P<0 .0 1) ;染毒至 30d时 ,血清中FSH水平在≥ 12mg/kg剂量范围继续呈现显著增加 (P <0 .0 1) ,睾丸匀浆中T在2 .4mg/kg剂量组则降低 (P <0 .0 5 )。ACP活性在染毒 15d时 2 .4mg/kg剂量组表现为升高 (P <0 .0 5 ) ,继续染毒至 30d时 6 0mg/kg剂量组则显著减低 (P <0 .0 5 ) ;γ GT活性则始终随染毒剂量的增加而降低 (P <0 .0 5 )。Spr与染毒剂量有明显的剂量依赖关系 ,在≥ 12mg/kg剂量范围显著减少 (P <0 .0 1)。 　结论 :Fen对雄性大鼠有明显的生殖毒性 ,可影响其血清及睾丸性激素水平和酶活性 ,这可能与Fen对支持细胞和生精上皮的损害有关     

苯甲酸雌二醇诱导不育小鼠睾丸中生精细胞增殖紊乱的研究

目的:探讨外源性雌激素苯甲酸雌二醇(EB)对诱导雄性不育小鼠中生精细胞增殖紊乱的影响。方法:60只雄性昆明小鼠随机分为3组,对照组肌肉注射150μl玉米油,EB处理组注射浓度分别为5、10 mg/kg的EB,隔天1次,持续4周。实验结束后取睾丸称其质量并计算睾丸指数;睾丸、附睾尾常规石蜡切片,HE染色;附睾尾制备精子悬液进行精子计数;免疫组化检测睾丸PCNA表达;qRT-PCR分析睾丸细胞周期蛋白A1、细胞周期蛋白B1、VASA、p53的表达变化;Western印迹检测p53及磷酸化p53蛋白表达。结果:与对照组相比,EB处理组小鼠睾丸指数显著下降[(0.56±0.09)%vs(0.43±0.08)%、(0.38±0.10)%,P0.05],精子悬液镜下观察未见精子,HE染色附睾管内未见精子;生精小管中精原细胞、初级精母细胞及支持细胞数量显著下降(P0.05)。免疫组化结果显示,与对照组相比,EB处理组生精小管中细胞PCNA阳性表达细胞数量显著下降(P0.05)。qRTPCR结果表明EB处理组PCNA、细胞周期蛋白A1、细胞周期蛋白B1、VASA mRNA表达与对照组相比显著下降(P0.05);p53表达随EB剂量升高而显著升高(P0.05)。Western印迹结果显示,与对照组相比,EB处理组p53及磷酸化p53蛋白表达水平显著升高,且存在剂量依赖效应,10 mg/kg组显著高于5 mg/kg组(P0.05)。结论:EB以剂量依赖的方式下调细胞周期相关因子表达抑制生精细胞的增殖,是导致雄性不育小鼠睾丸中生精细胞增殖紊乱的重要原因。     

醋酸铅对雄性小鼠生殖功能的毒性作用

目的　探讨醋酸铅对雄性小鼠生殖功能的毒性作用。　方法　不同浓度醋酸铅 ( 1 .5、6及 2 4mg/kg)腹腔注射 4周龄雄性小鼠 ,共 1 0次。 50d后与正常雌鼠合笼交配 ( 1∶2 ) ,观察雌鼠受孕率、胚胎总数、异常胚胎数 (率 )、胎鼠重量 ;测定睾丸指数、附睾精子数量、精子活动率和精子畸形率。　结果　对照组、醋酸铅各组合笼 2 1d,雌鼠受孕率和胚胎总数无显著差异 (P >0 .0 5)。醋酸铅 2 4mg/kg组异常胚胎数 (率 )显著高于对照组和 1 .5mg/kg组 (P <0 .0 5) ,胎鼠重量和雄鼠睾丸指数显著低于对照组 (P <0 .0 5)。其他实验组异常胚胎率、胎鼠重量和雄鼠睾丸指数与对照组比较无显著性差异。各实验组附睾精子数显著低于对照组 (P <0 .0 5,P <0 .0 0 5) ,附睾精子畸形率显著高于对照组 (P<0 .0 5,P <0 .0 0 5) ,中、高浓度醋酸铅组附睾精子活动率显著低于对照组 (P <0 .0 5)。　结论　醋酸铅 2 4mg/kg处理雄鼠对睾丸、精子数量和质量、合笼雌鼠胚胎产生影响。 1 .5及 6mg/kg只影响精子数量和质量而不影响生殖功能和子代。合笼雌鼠异常胚胎率增高和胎鼠重量下降可能与醋酸铅引起精子质量下降有关     

内皮素对大鼠睾丸间质细胞睾酮生成的影响

本研究采用大鼠睾丸间质细胞体外培养的技术 ,观察了内皮素 1对离体间质细胞睾酮分泌的影响。研究发现 ,10 -9mol/L的ET 1可显著抑制间质细胞睾酮的基础分泌 (P <0 .0 5 ) ,并且ET 1对人绒毛膜促性腺激素 (hCG)刺激睾丸间质细胞睾酮分泌也有抑制作用 ,其有效抑制浓度为 10 -10 mol/L(P <0 .0 5 )。本实验结果提示 ,ET 1呈剂量依赖性抑制睾丸间质细胞睾酮的基础分泌和hCG诱导的分泌 ,ET 1可能为睾丸内的一种局部调节多肽     

氰戊菊酯对大鼠精子及生殖激素的影响

目的探讨氰戊菊酯(Fen)对雄性大鼠精子计数、活力以及生殖激素的影响。方法成年雄性SD大鼠,分别以0、20、40、80mg/kg剂量的Fen连续灌胃染毒15和30d,按常规方法进行精子计数和精子活力检测,应用放射免疫法和化学发光免疫法测定大鼠血清卵泡刺激素(FSH)、黄体生成素(LH)、睾酮(T)、雌二醇(E2)和睾丸匀浆中T、E2水平。结果Fen染毒15d时,与0mg/kg组相比,40mg/kg剂量组精子数量明显减少(P<0.01),20和40mg/kg组睾丸匀浆中T水平显著降低(P<0.01,P<0.05),血清LH、FSH水平随染毒剂量的增加而升高,且FSH水平和染毒剂量有显著的剂量-效应关系(P<0.05);Fen染毒至30d时,各组间精子数量差异不显著,与0mg/kg组相比,40mg/kg剂量组(a+b)级精子活力显著降低(P<0.05),血清LH、FSH水平随染毒剂量的增加而升高,但差异不显著。结论Fen对雄性大鼠有明显的生殖毒性作用,能够改变血清和睾丸中的生殖激素水平。     

补肾助阳方对植物雌激素致勃起功能下降干预的实验研究

目的:研究补肾助阳方(养精胶囊)对大鼠阴茎勃起功能的影响机制。方法:成年雄性SD大鼠56只,随机分为7组,分别为空白对照组、大豆黄酮组、十一酸睾酮组、西地那非组及养精胶囊(高/中/低)剂量组。空白对照组给予生理盐水灌胃,其余各组100 mg/(kg·d)大豆黄酮灌胃30d。随后各实验组在给予大豆黄酮灌胃的同时,养精胶囊(高/中/低)剂量组分别给予1.26、0.63、0.315 mg/k/d剂量的养精胶囊组方,十一酸睾酮组给予4mg/(kg·d)剂量的十一酸睾酮,西地那非组给予2.5 mg/(kg·d)剂量的西地那非。分别在实验第0、30、60天观察各组大鼠阿扑吗啡诱导的自发勃起反应,记录勃起次数及勃起潜伏期,测定大鼠血清睾酮、黄体生成素水平,并观察大鼠阴茎海绵体组织切片。结果:实验第30天时,所有实验组大鼠阿扑吗啡诱导的勃起次数明显下降,勃起潜伏期延长,有统计学意义(P0.05)。第60天时,大豆黄酮组(1.39±0.42 vs 2.67±0.33)和大豆黄酮及低剂量养精胶囊组(1.33±0.49 vs 2.83±0.61)大鼠阿扑吗啡诱导的勃起次数明显下降(P0.05);阿扑吗啡诱导的大鼠勃起潜伏期只有大豆黄酮组[(16.33±3.11)min vs(8.50±0.93)min]和大豆黄酮及低剂量养精胶囊组[(15.50±3.21)min vs(8.63±1.54)min]明显延长(P0.05),其余各组变化不明显。实验第30天时,所有实验组大鼠血清睾酮、黄体生成素均有显著下降(P0.05)。实验第60d时,大豆黄酮组[(5.34±0.89)ng/ml vs(1.24±0.30)ng/ml]和大豆黄酮及低剂量养精胶囊组[(5.28±1.12)ng/ml vs(2.07±0.76)ng/ml]血清睾酮变化有统计学意义(P0.05)。两组的黄体生成素由(3.62±0.37)ng/ml、(3.79±0.28)ng/ml变为(2.09±0.12)ng/ml、(2.17±0.33)ng/ml,显著下降(P0.05)。切片结果显示对照组大鼠阴茎海绵体内海绵窦数目多,血管清晰可见。大豆黄酮加睾酮组、大豆黄酮加西地那非组和大豆黄酮加中、高剂量养精胶囊组大鼠海绵体与正常对照组相比,海绵窦数目减少。大豆黄酮组和大豆黄酮加低剂量养精胶囊组大鼠海绵体内海绵窦明显减少,血管少见。结论:使用高剂量养精胶囊治疗后,大鼠阴茎勃起功能恢复,对由植物雌激素引起的勃起功能下降有良好疗效。     

Daidzein together with high calcium preserve bone mass and biomechanical strength at multiple sites in ovariectomized mice

As the prevalence of osteoporosis is increasing, and the adverse effects of hormone replacement therapy are evident, women are searching for natural alternatives such as soy isoflavones to help prevent postmenopausal osteoporosis. Daidzein is one of the most abundant isoflavones present in soy and it is unique as it can be further metabolized to equol, a compound with greater estrogenic activity than other isoflavones. The objective of this study was to determine the effects of purified daidzein in combination with high calcium (Ca) on preserving femur and lumbar vertebrae (LV1-LV4) bone mineral density (BMD) and biomechanical bone strength at three different sites (femur midpoint, femur neck and LV3) in ovariectomized mice. Sham (SH) mice (n = 12) received control diet (AIN93G) containing 2 g Ca/kg diet and ovariectomized mice were randomized to 1 of 6 groups (n = 12/group): OVX (2 g Ca/kg diet), HCa (25 g Ca/kg diet), HD (2 g Ca + 200 mg daidzein/kg diet), HDCa (25 g Ca + 200 mg daidzein/kg diet), LD (2 g Ca + 100 mg daidzein/kg diet) or LDCa (25 g Ca + 100 mg daidzein/kg diet) for 12 weeks. HDCa preserved femur and vertebrae BMD and biomechanical bone strength (at all three sites) compared to the OVX group, however, only femur yield load (at midpoint) was preserved to a level that was greater (P < 0.05) than HCa alone. Mice fed HD diet had greater (P < 0.05) femur BMD than OVX group, however, daidzein alone (HD) did not appear to preserve trabecular bone (i.e., vertebrae BMD and vertebra peak load). All mice fed daidzein produced equol and there were no uterotrophic effects of daidzein at either dose. Both daidzein and Ca attenuated the increase in serum IL-1beta observed in the OVX group. The results from this study suggest that the combination of daidzein and high Ca favorably affect cortical and trabecular bone as indicated by femur and lumbar vertebrae BMD and biomechanical strength but much of this effect is mediated by the high Ca diet. Further investigation is required to determine optimal dietary levels of daidzein and Ca with the long-term goal of developing a dietary strategy to prevent postmenopausal osteoporosis and related fragility fractures.     

大豆黄酮对睾酮诱导的大鼠前列腺增生预防作用的实验研究

目的:探讨大豆黄酮对雄激素诱导的大鼠前列腺增生的预防作用。方法:成年雄性SD大鼠36只,随机分为Ⅰ~Ⅵ组,每组6只。Ⅰ组(正常对照组)、Ⅱ组(模型组)给予1ml生理盐水、Ⅲ~Ⅵ组(低、中、高大豆黄酮组及阳性对照组)分别给予2、20、100mg/kg大豆黄酮及0.1mg/kg己烯雌酚灌胃,1次/d,连续90d。从第91d开始,Ⅱ~Ⅵ组分别皮下注射丙酸睾酮(7.5mg/kg,1次/d,连续10d)诱导前列腺增生。观测各组大鼠前列腺湿重、前列腺指数;HE染色观察前列腺组织变化情况;免疫组化方法检测大鼠前列腺内雌激素受体α、β(ERα、ERβ)表达的变化。结果:与模型组相比,低、中、高大豆黄酮组及阳性对照组的前列腺湿重与前列腺指数均有显著降低(P<0.05或P<0.01)。中、高剂量大豆黄酮组大鼠前列腺增生减轻更明显,表现为上皮变薄,腺腔内分泌物明显减少,间质减少。ERα在模型组的表达与其余各组无明显差异;ERβ在各剂量大豆黄酮组与模型组相比明显减少。结论:大豆黄酮对睾酮诱导的前列腺增生有一定预防作用。     

Effect of the ethanolic extract from Fagara tessmannii on testicular function, sex reproductive organs and hormone level in adult male rats

The effect of ethanolic extract of Fagara tessmannii, wide medicinal plants used on reproductive function in South Cameroon, was investigated in male rats. Twenty male sexually experienced rats (four groups) were orally treated with vehicle, 0.01, 0.1, 1 g kg(-1) BW per day of F. tessmannii (equivalent to 16.67 g, 33.33 g, 50 g, 66.66 g kg(-1) dry raw material) for 14 days, the upper limit dose without any clinical sign of toxicity was 2 g kg(-1). Fagara tessmannii extract negatively affected weight of accessory organs and significantly affected body weight gain at dose 1 g kg(-1) (P < 0.05) in treated rats. The weight of epididymis and seminal vesicle significantly decreased at low doses (0.01 g kg(-1)) while the prostate weight decreased at all doses (P < 0.05). The transit of spermatozoa in cauda epididymidis significantly increased at lower dose of 0.01 g kg(-1) (P < 0.05). In addition, F. tessmannii extract affected neither daily sperm production (DSP) and DSP per g nor sperm count in vas deferens and epididymis. The length of stages IX-I of the seminiferous tubule and serum testosterone level increased dose-dependently following 14 days of treatment (P < 0.05). The results suggest that F. tessmannii, 14 days after treatment, may improve spermatogenesis, testosterone level and sperm transit in cauda epididymidis but negatively impair reproductive organ activities.     

Exposure of juvenile rats to the phytoestrogen daidzein impairs erectile function in a dose-related manner in adulthood

Health benefits of isoflavones such as genistein and daidzein have led to an increasing interest in consuming soybeans or soy-containing food. However, possible adverse effects of such plant estrogens on the male reproductive system, particularly penile erection, have not been sufficiently evaluated. In previous research, we observed that exposure of adult rats to daidzein could attenuate apomorphine-induced erections. To identify the impact of daidzein exposure in early life on erectile function, we evaluated erectile capacity using an apomorphine-induced erectile test and determining intracavernous pressure after exposure of juvenile rats to daidzein at a dose of 2, 20, or 100 mg/kg for 90 days. Meanwhile, the levels of sex hormones, including testosterone, luteinizing hormone, and follicle-stimulating hormone, were determined. Both subtypes of the estrogen receptor (alpha and beta) in the corpora cavernosa were also detected immunohistochemically. When the rats were examined at adulthood, we observed that those animals treated with a medium (20 mg/kg) or high (100 mg/kg) dose of daidzein, but not with a low dose (2 mg/kg), showed lower plasma testosterone levels and attenuated erectile parameters, including apomorphine-induced erections and intracavernous pressure concomitant with markedly decreased expression of estrogen receptor beta in the corpora cavernosa. However, the penis still grew to its normal size, as in controls. Thus, these results suggested that exposure of juvenile rats to daidzein in a relatively large amount could adversely affect penile erection in adulthood.     

Isoflavones and their effects on the onset of puberty in male Wistar rats

This study was performed to determine how two of the most important isoflavones, genistein and daidzein, affect the gonadal axis in male prepuberal rats. One hundred and seventy‐five prepuberal male Wistar rats were allocated into seven groups: one control group and six experimental groups that were orally administered a high or low dose of genistein, daidzein or a mixture of both. Testosterone determination was assayed by EIA. The testes and body weights were measured, and the histology of the epididymis with the sperm content and epididymal sperm count were evaluated. In the control group, we observed an increase in the serum testosterone levels (>2.5 ng ml^?1) at the third week (52 days), which corresponded to the onset of puberty in these rats. The same increase in serum testosterone levels was observed at the fourth week in rats that received low doses of isoflavones; therefore, we concluded that the onset of puberty was delayed. At high doses, there was no significant increase in testosterone levels, which could be related to the fact that these male rats did not reach puberty. These findings were supported by the results obtained from the analysis of the epididymal content as well as the testes/body weight ratio.     

Androgenic effect of Mondia whitei roots in male rats

Aim: To determine the effect of the aqueous extract of Mondia whitei (Periplocaceae) roots on testosterone production and fertility of male rats. Methods: Adult male Wistar rats were used. In the acute study, 20 rats were randomly divided into 5 groups of 4 animals each. Four treated groups were administered orally a single dose of Mondia whitei (400 mg/kg) and the controls received a similar amount of distilled water. One group of animals were sacrificed by cervical dislocation 1,2,4 and 6 h after treatment, respectively. The controls were sacrificed at 6 h. Testicular testosterone was determined by radioimmunoassay. In the chronic study, 28 rats were divided at random into 4 groups of 7 animals each: Groups 1, 2 and 3 were given orally the plant extract (400 mg·kg-1·day-1) for 2, 4 and 8 days, respectively. The animals of Groups 1 and 2 were sacrificed 24 hours after the last dosing. The controls (Group 4) received the same amount of distilled water for 8 days. The fertility was assessed only in Grou     

腺嘌呤制作雄性Wistar大鼠肾阳虚型不育症动物模型最佳时效和量效的小样本研究

目的:探讨阿拉伯胶助溶后的腺嘌呤对Wistar大鼠生殖毒性的时效和量效关系。方法:将腺嘌呤按0、50、100、150、200mg/ml浓度配制,按与腺嘌呤1:10比例加入阿拉伯胶作为助溶剂,1ml/(100g.d)剂量灌胃,共分5个剂量组;每10d各剂量组处死1批,每组每批5只,共3批。观察大鼠一般状态,分析精子质量、称量体重及生殖器官重量、进行病理检查、用放免法检测性激素的变化,并对腺嘌呤生殖毒性的时效和量效关系进行比较分析。结果:随着腺嘌呤给药时间的延长和剂量的增加,第3d各剂量组肾阳虚体征开始逐渐出现,100mg/(100g.d)剂量组灌胃10d开始,空白对照组比较,精子密度和活力、T、LH水平等各项指标出现明显降低(P<0.05或P<0.01),各给药组睾丸病理均出现轻重不同的病理变化,并呈一定的时效和量效关系。而50mg/(100g.d)剂量组自20d开始出现上述改变。结论:腺嘌呤法制作雄性Wistar大鼠肾阳虚型不育症动物模型最佳剂量点和时间点为按50～100mg/(100g.d)剂量腺嘌呤连续灌胃10～20d。