健脾生血颗粒对大鼠生育力与早期胚胎发育毒性的影响

目的评价健脾生血颗粒对大鼠生殖能力及早期胚胎发育的影响。方法将176只SD大鼠按性别分层,采用随机数字表法分为对照组及健脾生血颗粒低、中、高剂量组,分别以健脾生血颗粒0、1.16、3.48、5.80 g/(kg·d)给予雌鼠2周及雄鼠4周连续灌胃给药后,雌雄大鼠以1∶1合笼,雌鼠持续给药至妊娠第7天,雄鼠持续给药至剖检前,雄鼠整个给药周期为59~63天。剖检所有亲代动物,观察亲代动物体征形态,检查组织病理情况进行一般毒性检测;称重睾丸、附睾,计数附睾尾精子数并行精子活力检查检测生殖力毒性;计数黄体、活胎、死胎、吸收胎并计算着床数以观察早期胚胎发育毒性。结果 (1)一般毒性:健脾生血颗粒高剂量组雄鼠体重增长减缓。中低剂量组则无异常;(2)生育力毒性:健脾生血颗粒各剂量对雄鼠睾丸、附睾及附睾尾精子数量均无明显影响;(3)早期胚胎发育毒性:健脾生血颗粒各剂量组对早期胚胎形成未见明显影响。结论健脾生血颗粒一般毒性方面可能存在一定的胃肠毒性作用,未见毒性反应剂量为3.48 g/(kg·d)。健脾生血颗粒各剂量组均未见明显生育力及早期胚胎发育毒性反应。     

雄黄灌胃给药对大鼠生育力与早期胚胎发育毒性的研究

目的观察中药雄黄灌胃(ig)给药对大鼠生育力与早期胚胎发育的毒性影响。方法 SD雌雄大鼠分为阴性对照组,雄黄低、中、高剂量组4组,雄性大鼠连续ig给药6周后与连续给药2周的雌鼠交配,每天ig给予批号为H2007052401雄黄250、125和50 mg.kg-13个剂量。雄性给药至交配全部结束,雌性给药至妊娠第6天。雄鼠交配后处死,雌鼠妊娠第15天处死,计算黄体数、着床数、活胎数等,并与阴性对照组比较。结果雄黄各剂量组动物的交配率、受孕率、活胎率、着床前后丢失率、黄体数、着床数以及生殖脏器方面与阴性对照组比较均未有显著差异;病理组织学方面:所有高剂量组及对照组动物的睾丸、附睾、卵巢未见明显异常。结论批号为H2007052401雄黄在本实验中对大鼠生育力和早期胚胎发育没有明显的毒性作用。     

染料木素对大鼠生殖毒性的实验研究 (Ⅰ)一般生殖毒性

目的为保证染料木素临床用药的安全,评价其生殖毒性.方法16,160,480 mg/(kg·d)染料木素分别连续ig雄、雌性大鼠60 d,14 d后合笼,雄性大鼠给药至交配结束,雌性大鼠给药至妊娠第17天,观察染料木素对大鼠的受胎能力、生殖系统及子代的影响.结果染料木素480 mg/(kg·d)引起亲代雄性大鼠精子活动度下降,但未发现睾丸病变,也未影响雄鼠生殖能力;同时使雌鼠妊娠期体重增长明显低于其他组(P＜0.01),但未影响胚胎形成、仔鼠生长发育.160 mg/(kg·d)剂量对亲代和子代未引起明显的异常.结论染料木素160 mg/(kg·d)对雌、雄性大鼠无一般生殖毒性作用.     

云南白药对大鼠生育力与早期胚胎发育毒性的影响

目的：评价云南白药对大鼠生育力及早期胚胎发育的毒性影响。方法：SD大鼠每天分别灌胃给予云南白药4.0、1.4、0.5g.kg-1剂量和超纯水（以下简称＂阴性对照＂）1.5mL.kg-1。每天1次,连续给药4周和2周后将雄鼠和雌鼠按1∶1合笼,交配14d,记录交配情况。雄鼠给药至交配结束,雌鼠给药至妊娠第6天。在整个试验过程中每天观察大鼠的一般反应,定期称量大鼠体重和摄食量。雌雄大鼠分别于妊娠第15天和交配结束后进行解剖检查,计算孕鼠黄体数、着床数、活胎数、死胎数吸收胎数等检查早期胚胎发育情况,睾丸、附睾、前列腺或卵巢、子宫称重并计算脏器系数。结果：云南白药3个剂量组分别与阴性对照组比较,各剂量组雄鼠体重增长缓慢,有剂量和时间关系,雌鼠体重增长无异常;仅高剂量组大鼠的摄食量略少于阴性对照组;高剂量组给药后出现流涎、活动减少、闭眼等症状,少数大鼠出现打喷嚏、挠嘴等反应;各组大鼠解剖脏器均未发现肉眼可见的异常;各剂量组交配率、妊娠率、合笼天数与阴性对照组均无显著性差异P〉0.05;子宫连胎重、黄体数、着床数、着床前丢失数、活胎数、死胎数、吸收胎数等胚胎形成指标与及阴性对照组比较均无显著性差异;高剂量组睾丸系数、附睾系数、前列腺系数,中、低剂量组附睾系数高于阴性对照组（P〈0.05或P〈0.01）。结论：在本试验剂量条件下,SD大鼠从交配前到交配期直至胚胎着床期间灌胃给予云南白药,对雌雄大鼠有一定的亲代毒性作用,但并不影响大鼠的生育力及早期胚胎发育,大鼠的生育力及早期胚胎发育毒性的无毒性反应剂量（NOAEL）为4.0g.kg-1。     

二五四合剂对环磷酰胺致小鼠生精障碍的治疗作用

目的观察二五四合剂对环磷酰胺致小鼠生精障碍的治疗作用。方法将小鼠随机等分为4组:模型组,对照组,小、大剂量二五四合剂组。除对照组外,其余各组小鼠腹腔注射环磷酰胺建立生精障碍模型。造模后,小、大剂量二五四合剂组小鼠分别给予3 g/kg、9 g/kg剂量二五四合剂灌胃,模型组与对照组小鼠灌胃等量生理盐水,连续25 d。测定各组小鼠与雌鼠合笼后的胚胎数、睾丸质量、精子密度、活率及畸形率。结果模型组小鼠睾丸质量、精子参数、与雌鼠合笼后的胚胎数均差于对照组小鼠(P0.05);各剂量二五四合剂组小鼠睾丸质量、精子参数、与雌鼠合笼后的胚胎数均优于模型组小鼠(P0.05);与对照组比较,大剂量二五四合剂组小鼠睾丸质量、与雌鼠合笼后的胚胎数无显著差异(P0.05)。结论二五四合剂可有效治疗环磷酰胺所致小鼠生精障碍。     

染料木素对大鼠生殖毒性的实验研究（I）一般生殖毒性

目的　为保证染料木素临床用药的安全 ,评价其生殖毒性。方法　 16,160 ,480 mg/(kg· d)染料木素分别连续 ig雄、雌性大鼠 60 d,14 d后合笼 ,雄性大鼠给药至交配结束 ,雌性大鼠给药至妊娠第 17天 ,观察染料木素对大鼠的受胎能力、生殖系统及子代的影响。结果　染料木素 480 mg/(kg· d)引起亲代雄性大鼠精子活动度下降 ,但未发现睾丸病变 ,也未影响雄鼠生殖能力 ;同时使雌鼠妊娠期体重增长明显低于其他组 (P<0 .0 1) ,但未影响胚胎形成、仔鼠生长发育。 160 mg/(kg· d)剂量对亲代和子代未引起明显的异常。结论　染料木素 160 mg/(kg·d)对雌、雄性大鼠无一般生殖毒性作用     

杞椇颗粒剂对雄性大鼠酒精性性功能损伤的预防作用

目的:观察杞椇颗粒剂对雄性大鼠酒精性性功能损伤的预防作用。方法:大鼠随机分为杞椇颗粒剂14g/kg、7g/kg、3.5g/kg组,睾酮4mg/kg组,模型对照组和正常对照组。各给药组动物均灌胃给予56°白酒10ml/kg,同时给予相应药物,正常对照组灌胃等体积蒸馏水,连续45天。各给药组雄鼠均分别与动情期雌鼠1∶1合笼,记录初次发现阴栓时间,阴栓数,交配率。合笼完成后,检测雄鼠血清睾酮水平,计算睾丸、附睾、精囊腺、肾脏等脏器指数。于妊娠第18天处死雌鼠,计算受孕率、胎鼠窝均体重、胚胎吸收率、活胎率、死胎率;将胎鼠做骨骼染色,计算骨骼发育不全率。结果:杞椇颗粒剂14g/kg、7g/kg、3.5g/kg剂量组睾丸指数分别为0.84±0.04、0.88±0.07、0.87±0.04 g/100g均高于模型对照组0.79±0.07 g/100g(P0.05或P0.01),附睾指数分别为0.33±0.03、0.34±0.04、0.36±0.32 g/100g均高于模型对照组0.29±0.02 g/100g(P0.05或P0.01),精囊腺指数分别为0.37     

枸杞多糖对低雄激素不育模型大鼠影响的药效观察和作用机制研究

目的通过观察枸杞多糖对低雄激素不育大鼠生殖损伤的改善作用,评价枸杞多糖治疗低雄激素雄性不育的药效和可能的作用机制。方法将雄性成年SD大鼠随机分为空白对照组、模型对照组、枸杞多糖低剂量和高剂量组,其中造模给药方式为灌胃给予度他雄胺40 mg/kg,1次/d,连续28 d;在造模的第15天开始枸杞多糖干预灌胃给药,高低剂量组分别给予枸杞多糖80 mg/kg和40 mg/kg,模型对照组给予等量溶媒,1次/d,连续14 d。给药结束时检测睾丸附睾组织学、超微结构、精子活力、交配雌鼠受孕率、血清雄激素水平、附睾雄激素受体(AR)和核转录因子(NF-κB)蛋白表达。结果与模型对照组比较,枸杞多糖高剂量组精子活率和前向运动率显著升高(P0.05);枸杞多糖低剂量组和高剂量组交配雌鼠受孕率分别为37.5%和62.5%,较模型对照组分别上升25%和50%;模型对照组附睾可见附睾上皮连接出现断裂,管内精子聚集;枸杞多糖低剂量组大鼠附睾上皮结构和精子排列有一定的恢复,高剂量组附睾上皮组织和精子基本恢复正常;枸杞多糖给药组血清双氢睾酮(DHT)水平较模型对照组显著升高(P0.05,P0.01);枸杞多糖给药组AR和NF-κB蛋白表达较模型对照组显著升高(P0.05,P0.01)。结论枸杞多糖可以改善低雄激素附睾不育大鼠的生育能力,其作用机制可能与升高血清DHT水平、促进AR和NF-κB表达、发挥雄激素样活性有关。     

锁阳蜜干预雷公藤多甙对小鼠生育影响的研究

目的：观察不同时间和剂量的雷公藤多甙（GTW）对昆明小鼠怀孕率的影响;锁阳蜜（CSR）干预和停用GTW后的自愈倾向。方法：空白组小鼠给1％羧甲基纤维素（CMC）溶液;GTW分为5个剂量组,灌服45mg／kg、30mg／kg、22．5mg／kg、15mg／kg、7．5mg／kg的GTW混悬液;联合组为锁阳蜜水煎剂3．9g／kg＋GTW7．5mg／kg、7．8mg／kg＋GTW30mg／kg,停药组给30mg／kgGTW混悬液,以上各组先灌胃20d。20d后与成年雌鼠1：2合笼7d。第28d起各组按照剂量继续给药,停药组停用GTW。20d后再次合笼7d。每次合笼后观察雌鼠怀孕率。结果：随着GTW给药时间的延长和剂量的增加雌鼠怀孕率呈下降趋势。45mg／kg组给药40d后怀孕率降为0％（P〈0．01）。锁阳蜜7．8g／kg组怀孕率由20d时的20％上升到40d时的65％。停药组怀孕率由20％上升到55％,与同一时间段的GTW组比较P〈0．05,与空白组比较P〉0．05。结论：GTW对雄性小鼠的生殖毒性是呈时间依赖和剂量依赖的。锁阳蜜可以改善GTW对雄鼠生殖系统的抑制作用,提高雌鼠的怀孕率。停用GTW20d,怀孕率可以基本恢复正常。     

野山楂根拮抗雷公藤多苷对雄性大鼠生殖损伤作用的研究

目的:观察中药野山楂根水煎剂对雷公藤多苷所致雄性不育大鼠生育力的影响。方法:将成年雄性大鼠随机分组,分别给予雷公藤多苷片溶液(10 mg.kg^-1),野山楂根水煎剂(1.8,5.4,18 g.kg^-1)+雷公藤多苷片溶液(10 mg.kg^-1)和蒸馏水(1 mL.kg^-1)灌胃,8周后停用雷公藤多苷,中药组继续行野山楂根灌胃。4周后各组动物与成年雌性大鼠交配,观察交配雌鼠妊娠率和平均胚胎、黄体数。测定雄鼠生殖器官性腺脏器指数、附睾精子计数、活力、存活率,观察各组动物睾丸、附睾组织病理和超微结构改变,放射免疫法测定血清和睾丸组织睾酮(T),血清卵泡刺激素(FSH)和促黄体生成素(LH)含量。结果:与雷公藤多苷模型组比较,野山楂根组交配雌鼠妊娠胎数、雄鼠睾丸、附睾脏器指数以及附睾精子计数、活力均有提高(P<0.05);野山楂根组精子超微结构较模型组有明显恢复;睾丸组织匀浆T显著高于模型组(P<0.01)。结论:野山楂根能够拮抗雷公藤多苷对雄性大鼠的生殖损伤作用,提高不育症模型雄鼠的生育力。     

合成冰片对大鼠肝CYP450酶含量及CYP3A1 mRNA表达的影响

[目的]研究冰片对大鼠肝脏细胞色素氧化酶（cytochromeP450,CYP450）含量及其亚型CYP3AImRNA表达的影响。[方法] Wistar大鼠合成冰片（设0．3g／kg和0.03g／kg剂量组,1次／d,连续7d）灌胃,以溶媒羧甲基纤维素纳（CMC-Na）和苯巴比妥钠为对照组,钙沉积法提取肝微粒体,紫外分光光度法测定CYP450含量,实时定量RT-PCR法检测肝脏CYP3AImRNA的表达。[结果]0．3g／kg合成冰片口服可诱导大鼠肝脏CYP450酶含量增高（P〈0．05）,CYP3A1 mRNA表达上调（P〈0．05）。[结论]高剂量合成冰片口服可能影响肝脏药物代谢。     

伤科黄水经口给药的长期毒性研究

摘 要 目的:观察连续灌胃给予伤科黄水后,SD大鼠产生的毒性反应及其严重程度。方法:将SD大鼠按体重和性别随机均衡分为4组,分别为空白对照组,伤科黄水4.58 g/kg剂量组、9.16 g/kg剂量组、18.33 g/kg剂量组,每组8只,雌雄各半。各组均以10 ml/kg灌胃给药,每天给药1次,连续给药14 d。试验期间,每天观察大鼠的外观体征、行为活动、腺体分泌、呼吸、粪便性状等。在给药第1、4、7、11、14天测定大鼠体重。在剖检前一天（给药第14天）进行尿液、眼科检查。剖检当天处死全部大鼠,进行脏器检查。结果:与空白对照组相比,给药第14天伤科黄水18.33 g/kg剂量组雌性动物的体重（P＜0.05）和14天内的增重（P＜0.01）均明显下降,其余各组无明显变化。各组动物眼科检查均未见异常。伤科黄水4.58 g/kg剂量组、9.16 g/kg剂量组、18.33 g/kg剂量组雄性动物尿比重高于空白对照组（P＜0.05或P＜0.01）,尿液pH值低于阴性对照组（P＜001）,其余各组无统计学差异。伤科黄水18.33 g/kg剂量组雌性动物胸腺脏器重量、脏体系数、脏脑系数低于空白对照组（P＜0.05或P＜0.01）,心脏脏器重量低于空白对照组（P＜0.05）,伤科黄水9.16 g/kg剂量组睾丸脏脑系数低于空白对照组（P＜0.05）,其余各组无统计学差异。结论:伤科黄水重复多次口服给药未发现明显毒副作用。     

薄荷醇及冰片对磺胺嘧啶和伊文思蓝在脑中分布的影响

薄荷醇（ｉｇ１０％薄荷醇石蜡油液１５ｍｌ／ｋｇ）及冰片（ｉｇ１０％冰片石蜡油液１５ｍｌ／ｋｇ）可明显延长磺胺嘧啶在大鼠体内分布相半衰期ｔ１／２ａ，增加磺胺嘧啶在大鼠脑内的浓度。薄荷醇、冰片（ｉｇ０．５ｇ／ｋｇ×４ｄ）还可使伊文思蓝透过小鼠血脑屏障，　但其透过量远明显低于夹闭双侧颈动脉再灌注脑损伤组。以上结果提示，薄荷醇、冰片可能具有促进Ｓｕｌ透过血脑屏障，而对血脑屏障结构的损伤可能性小。     

Reproductive toxicology and clastogenic evaluation in mice of a phytotherapeutic formulation obtained from Cinchona calisaya Weddel (Rubiaceae) used in Brazilian folk medicine as female fertility stimulant

Ethnopharmacological relevance

In Brazil, a phytotherapeutic preparation produced from a standardized tincture of Cinchona calisaya Weddel such that each mL of product contains 400 µg of quinine, known in Portuguese as Água Inglesa^® (English water), is indicated by the manufacturer as a tonic, appetite stimulant, and digestive. However, this preparation has long been used in folk medicine as a female fertility stimulant. Despite its widespread use in folk medicine to stimulate female fertility, no study has been undertaken to assess the potential teratogenic and genotoxic effects of this phytotherapeutic preparation. The aim of the present study was to investigate possible toxic reproductive effects in mice caused by exposure to Água Inglesa^®, either before mating or during the pre- and post-embryo implantation periods. The genotoxic potential was evaluated using the micronucleus assay.

Material, Methods, and Results

Virgin female mice, with at least one estrous cycle evidenced by vaginal cytology, were divided into five groups of 15 individuals each (Group I – control, Group II – treated with ethanol solution at 16%, Groups III, IV and V treated with phytotherapeutic preparation at 1.5 mL/kg/day, 3.0 mL/kg/day and 4.5 mL/kg/day, respectively). After the first 28 days of treatment, females were caged individually with adult fertile males. Pregnant females continued to receive treatment for seven days (preimplantation period). Body weight was recorded weekly during treatment. Signs of toxicity (weight loss, food intake, piloerection, apathy, prostration, diarrhea, seizures, behavioral changes, and locomotion) were also observed. The females were sacrificed on the 15th day of pregnancy, uterine horns were evaluated for implantation, and the placental index was recorded. In the micronucleus test, 2000 polychromatic erythrocytes (PCE) per animal, obtained from bone marrow, were scored. Results The results showed that exposure of the females during the pre- and post-implantation periods did not significantly alter the reproductive capacity (p<0.05); however, in higher dose (three times human dose)reduction of fetal weight was observed . There was no difference between the control and phytotherapeutic preparation (p>0.05) in terms of the average number of micronucleated polychromatic erythrocytes.

Conclusions

Although folk medicine suggests that the Água Inglesa^® preparation is useful as a female fertility stimulant, no such effect was confirmed in mice.     

四子种王胶囊治疗雄性不育大鼠实验研究

目的观察四子种王胶囊治疗雄性不育大鼠模型的效果。方法将80只Wistar大鼠随机分为4组,即正常对照组、模型对照组及四子种王胶囊大、小剂量组,各20只。正常对照组予蒸馏水3 mL,每日1次灌胃;其余3组均予腺嘌呤25 mg/100 g体质量,以蒸馏水3 mL配制后,每日1次灌胃。各组均连用30 d。造模结束后,正常对照组和模型对照组均予蒸馏水3 mL,每日1次灌胃;四子种王胶囊大、小剂量组分别予四子种王胶囊6、3 g/kg体质量,以蒸馏水3 mL制成混悬液,每日1次灌胃。各组均连用30 d。进行生育力、生殖激素、附睾精液质量、附睾精子精核蛋白（RP）、组蛋白（TH）的测定。结果四子种王胶囊大、小剂量组配对雌鼠受孕率均高于模型对照组（P〈0.01）。四子种王胶囊大、小剂量组黄体生成激素（LH）、睾酮（T）均较模型对照组显著升高（P〈0.01,P〈0.05）,各组间FSH比较差异均无统计学意义（P〉0.05）。四子种王胶囊大剂量组精子密度、精子存活率及精子活动力（a级）,四子种王胶囊小剂量组精子密度及精子活动力（a级）均高于模型对照组（P〈0.01）。四子种王胶囊大、小剂量组TH相对含量、TH/RP均低于模型对照组（P〈0.01）,RP相对含量均高于模型对照组（P〈0.01）。结论雄性不育大鼠经四子种王胶囊治疗后,生育力提高,精液质量改善,LH、T有不同程度上升,RP相对含量明显改善。     

Contraceptive efficacy of Carica papaya seed extract in male mice (Mus musculus)

The effects of an aqueous extract of Carica papaya seeds (20 mg/kg body weight/animal/day orally and 5 mg/kg body weight/animal/day i.m. for 60 days) were investigated for contraceptive efficacy and other related side effects in male albino mice, Mus musculus. The data revealed that the extract might be causing an androgen deprived effect to target organs resulting in alterations in the internal milieu of the cauda epididymis especially. The treatment did not, however, affect the testicular sperm count suggesting that it acted at the post-testicular level which lead to a reduction of cauda epididymal sperm motility and thus the treatment brought about a significant reduction in fertility rate. The induced effects were transient and reversible upon withdrawal of the treatment, elucidating that functional sterility could be induced by the aqueous papaya seed extract in rodents.     

Male rat infertility induction/spermatozoa and epididymal plasma abnormalities after oral administration of Kalanchoe gastonis bonnieri natural juice

Natural aqueous crude extracts (NACE) of several Crassulaceae family plants have been applied as a vaginal contraceptive by the populace. The aim of this work was to evaluate the inhibition of fertility in male Wistar rats and some physiological and biochemical changes in spermatozoa and epididymal plasma induced by NACE from Kalanchoe gastonis bonnieri (K. g. b.) (Crassulaceae). The NACE was obtained by mechanic pressure on grinding fresh plant leaves. Sublethal doses (150-300 mg/kg body weight) of NACE were orally administered to adult and fertile male rats daily for 30 days in a search for a contraceptive effect, and physiological and biochemical modifications on sperm cells and cauda epididymal plasma. The toxicity studies revealed that the lethal dose (LD(50)) calculated was 11 g/kg body weight. Sublethal doses induced 50%-100% fertility inhibition, with 100% recovery of fertility 30 days after stopping the treatment. The sperm motility, viability and spermatic density were also significantly decreased (p < 0.001). The outstanding biochemical change observed in the cauda epididymal plasma was a decrease of carnitine concentration. The NACE of K. gastonis contains one substance active on fertility by affecting spermatozoa motility, viability and sperm density with a significantly decreased carnitine and sialic acid (p < 0.001) in the caudal epididymal plasma.     

Gangetin—a reproductive inhibitor in male rats

Gangetin, a plant pterocarpan when administered subcutaneously to adult male rats at a dose of 2 mg/kg body weight/day for 56 days caused a significant reduction in mating rate. Also a decrease in the weight of the testes and accessory sex organs, a decrease in fructose content of the coagulating gland and a reduction in acid phosphatase activity in the prostate were observed. All these effects were found to be reversed by exogenous prolactin (500 μg/kg body weight/day) plus testosterone propionate (200 μg/kg body weight/day), but not by prolactin or testosterone alone, when administered along with gangetin for the last 28 days. An inhibitory influence of gangetin over the reproductive organs is believed to be attributed primarily to the antiprolactin nature of gangetin and secondarily to the significant (p <0.001) fall in plasma testosterone level caused by gangetin. © 1997 John Wiley & Sons, Ltd.     

Effects of Rubus coreanus on sperm parameters and cAMP-responsive element modulator (CREM) expression in rat testes

Rubi Fructus (RF), the dried, unripe fruit of Rubus coreanus M IQ. (Rosaceae), has been used to improve male reproductive function in traditional Korean medicine. In this study, we investigated the effects of RF on sperm parameters and expression of cAMP-responsive element modulator (CREM), which has a crucial role in spermatogenesis. RF was administered to 8-week-old male Wistar rats for 56 consecutive days (1.0 g/kg, daily, p.o.). Sperm analysis, RT-PCR, and Western blot assays were then carried out. The RF-treated animals showed significant increases in the weight of the testes, epididymal sperm count, and sperm motility compared to the control group. RF also increased the expression of CREM at both the mRNA and protein levels. These results suggest that RF may improve male fertility by enhancing spermatogenesis.