蓖麻油抗雌鼠生育作用活性物质的分离、分析及作用机理研究
|
摘要
鼠害是农业生物灾害中的主要灾种之一，是当今世界性灾害，给农业、林业、畜牧业等造成了巨大的经济损失。有效控制鼠害是保障农林牧业可持续发展的关键环节。目前，国内外鼠害防治以化学防治为主，主要是通过增加鼠的死亡率来控制害鼠的种群数量，但均无持效性，且灭鼠后的低密度时间最长仅维持一年左右，此后鼠密度逐渐上升而恢复至原有水平；传统灭鼠剂还存在对环境和其它生物有毒副作用和成本高等弊端。鉴于传统灭鼠措施存在的不足，一种新的鼠害控制策略逐渐受到重视，即从保持生态平衡的角度出发，寻求一种控制鼠类出生率的植物性不育剂，通过降低鼠类群体的繁殖率而实现降低群体密度，从而达到从根本上控制鼠害的目的，且对人类和其他动物、环境安全无害，效果持久。
有关不育对鼠类种群繁殖力和数量影响的研究表明：不育能够取得灭杀的效果，若考虑不育的干扰作用，不育方法比灭杀更能控制鼠类种群数量的增加；不育控制鼠害的实验表明，雌性不育比雄性不育效果好，而双性不育比单性不育效果更好。在近年来兴起的植物不育剂的研究和开发中，许多植物源不育剂是针对抗雄鼠生育的，而抗雌鼠生育植物不育剂的研究和开发却较少见。其主要原因是在雌性不育剂有效成分的研发过程中，作为导向分离的筛选靶标较难确定，造成筛选抗雌鼠生育有效成分难度比较大。
蓖麻油是大戟科植物蓖麻(Ricinus communis L．)种子的乙醚提取物(AEC)。在我国传统医学中，蓖麻油具有泻下通滞、消除痈疽肿毒、导泻等功能；临床上用蓖麻油抄鸡蛋进行催产已有多年的历史；在印度、朝鲜、约旦等国和一些非洲国家，妇女常常服用蓖麻籽及其提取物来进行避孕。有研究表明，蓖麻油具有抗雌鼠和雄鼠生育的作用，且其抗生育活性较强。为了研制新型的鼠类不育剂，本研究对蓖麻油抗雌鼠生育作用和作用机理进行了研究，建立了抗雌鼠生育活性物质的体外筛选方法，导向分离出具有较强抗雌鼠生育活性的晶体物质，并对这一抗雌鼠生育活性晶体物质进行了分析。本论文研究的结果既为开发高效、安全的植物源抗鼠生育药物提供有效药源，又为我国蓖麻资源的综合利用开辟了新途径，有利于提高蓖麻产业经济效益与社会效益；有利于为创制与环境相容的高效植物源生物鼠不育剂、开发出具有我国自主知识产权的新型植物源农药，奠定坚实的理论基础。本论文主要研究内容和结果如下：
1、通过用蓖麻油在特定的时间内连续灌胃小鼠，统计怀孕率和胚胎数量，研究蓖麻油的抗早孕、抗着床作用。结果表明：20 mg/kg/d处理组小鼠受孕率降低不明显，但是小鼠所孕胎儿总数有一定的减少；40 mg/kg/d及其以上浓度的两个处理浓度小鼠受孕率明显降低，其生育抑制率分别达到：72.2％、88.2％和90％(与对照组比较，p<0.01)，个体所孕的胎儿数也明显减少；蓖麻油对小鼠的生育抑制作用有一定的量-效关系；在抗着床方面，40 mg/kg/d、80 mg/kg/d和160 mg/kg/d三个处理组的子宫内着床位点明显减少，着床率明显降低，分别为：3/8、1/6和1/6；在抗早孕方面，从40 mg/kg/d处理浓度开始，小鼠怀孕率明显降低，生育抑制率显著提高；小鼠怀孕的胎儿数随着处理浓度的增加而减少；此外，蓖麻油处理组卵巢和免疫系统主要的器官脾和肾上腺指数变化不明显，但从40 mg/kg/d处理浓度开始，小鼠胸腺增大、胸腺指数增加。随着处理浓度的加大，胸腺指数增加得越显著(p<0.01)。
2、采用灌胃蓖麻油后对小鼠动情周期、血清雌二醇(E2)、孕酮(P)等性激素水平和妊娠相关蛋白-A(pregnancy-associated plasma protein A，PAPP-A)变化情况，以及蓖麻油引起的未怀孕体质健壮小鼠的卵巢、输卵管和子宫结构变化进行研究，探讨蓖麻油抗生育活性的作用机理。结果表明：20mg/kg/d剂量蓖麻油处理组小鼠动情期的时间和表现与对照组比较均无明显区别；而40mg/kg/d及其以上处理组小鼠在动情期生理特征不明显，动情期缩短，动情间期延长且不规则。小鼠血清中的雌二醇(E2)水平无明显变化，而孕酮(P)含量有一定的升高；在20 mg/kg/d处理组，小鼠血浆中的PAPP-A稍微低于对照组；而从40 mg/kg/d处理剂量开始，PAPP-A值降低显著；且随着蓖麻油处理浓度的增加，PAPP-A值降低程度增大；蓖麻油40 mg/kg/d剂量处理组和以上浓度剂量处理组膨大子宫与正常对照未孕雌鼠子宫相比，其内腔扩大，子宫壁明显变薄；肌肉层比对照组薄，肌纤维排列疏松、紊乱：子宫基质层变薄，其内腺体减少；黏膜上皮增厚。
3、通过用不同剂量蓖麻油处理原代培养大鼠蜕膜细胞和黄体细胞，观察细胞形态变化，同时用MTT法检测细胞活力，确定了蓖麻油抗雌鼠生育活性成分的作用靶标，首次建立蓖麻油抗生育有效成分的体外筛选方法。结果表明：400μg/mL及其以上浓度蓖麻油处理液对体外培养大鼠蜕膜细胞形态有明显的影响，400μg/mL蓖麻油处理液使部分离体培养蜕膜细胞体积比正常细胞明显减小、细胞内出现明显空泡，部分细胞胞浆皱缩、死亡。MTT法检测发现：400μg/mL及其以上处理浓度的蓖麻油对蜕膜细胞的生长有显著的抑制作用(p<0.05)；蓖麻油对蜕膜细胞的半抑制浓度(IC_(50))为568.6±5.3μg/mL，r=+0.9790；且这一抑制作用具有良好的量-效关系。而蓖麻油对黄体细胞活力的抑制作用不显著，仅仅表现在600μg/mL浓度蓖麻油处理24h的大鼠黄体细胞体积变小，细胞数量略有减少。用大鼠离体培养蜕膜细胞的活力测定方法作为蓖麻油抗雌鼠生育有效成分分离、提纯的活性跟踪指标是可行的。
4、以原代培养大鼠蜕膜细胞(DSC)活力作为筛选靶标，首次导向分离蓖麻油(AEC)中的抗生育活性成分。经过皂化、乙醚萃取、乙醇重结晶和活力检测等步骤，获得一种对大鼠蜕膜细胞活力有抑制作用的无色晶体，其半抑制浓度(IC_(50))为63.84±3.04μg/mL，r=+0.9478。GC-MS分析和计算机相似性比较表明：无色晶体由5种成分组成，其中有4种成分为植物甾醇。5种成分分别是：麦角甾-5-稀-3-醇(Ergost-5-en-3-ol)，豆甾醇(Stigmasterol)，v-谷甾醇(γ-Sitosterol)、岩藻甾醇(Fucosterol)，和普罗布考(Probucol)类似物等。其中γ-谷甾醇(7-Sitosterol)的含量最高，达44.77％；其余组分的含量分别是：豆甾醇(Stigmasterol)占35.80％，岩藻甾醇(Fucosterol)占8.40％，麦角甾-5-稀-3-醇(Ergost-5-en-3-ol)占6.10％和普罗布考(Probucol)类似物占4.93％。根据实验结果和文献报道推测：γ-谷甾醇(7-Sitosterol)很有可能是抑制离体培养大鼠蜕膜细胞活力的主要成分；而豆甾醇(stigmasterol)可能起协助的作用。
Rodent pest is a worldwide calamity, which is one of leading disasters in the field of bio-agriculture. In China, tremendous economic losses in the fields of agriculture, forestry and animal husbandry are caused by Rodent pests. The effective control of rodents is of importance to ensure the agriculture sustainable development. Presently, the mainly rodents control method in the world is chemical control, most of the rodenticides mainly cause the increase of the mortality of mice and could not keep long effect, the low density of mice can maintain only one year, since the density of mice rise gradually and restore to the previous level. In addition, chemical rodenticides possess the side-effects on environment and living things. Due to the shortcomings of traditional rodenticides, the new rodenticide is urgently necessary for the efficacious and continuous reduction of mice: the population density of mice could be reduced by decreasing the reproduction rate of mice, namely, developing a new strategy of biological sterilization of rodents.
The results of the investigation on the effect of sterility on the rodent reproduction and their population demonstrated that: Decreasing the reproductive ratio instead of increasing mortality had been suggested as a promising means for managing the impact of overabundant species. Sterilized resident females were thought to restrict reproduction on the population level if they maintained their territories and social status and prevented subordinates from breeding. Many botanic sterilants development in recently years acted on male rodents, but few acted on female. The reason was that the choice of guide for bioassay-guided fractionation of antifertility components in female rodents was difficult.
Castorbean oil, an aether extract from the castorbean seeds(Ricinus communis L.)(AEC), has been known to possess medicinal property of antifertility activity on both female and male mammals. In order to developing new sterilants, the antifertility effect and the machinsm of castorbean oil in female rodents were investigated, the in vitro method for separating the contraceptive components of AEC was established; a colorless crystal which showed a significant inhibitory activity on rat decidual stormal cells was separated by means of bioassay-guided fractionation, and the colorless crystal was chemically analyzed. The results of the research not only supplied high-effective and safe botanic medicine for antifertility of rodents, but also established a new way of comprehensive utilization of castorbean resource of our country, which was beneficial to developing castorbean industry. It will helpful to the establishment of the substantial rationale for the developing of high-effective botanic antifertility medicine of our country possessing independent intellectual property rights, and also for the developing of the neotype botanic rodentcide. The main results are showed as follows.
1 Kunming mice were gavaged the AEC at doses of 0mg/kg/d, 20mg/kg/d, 40mg/kg/d, 80mg/kg/d and 160 mg/kg/d in specified time respectively. The amount of pregnancy mice and the embryos were added up for the research on the anti-early pregnancy and anti-implantation of AEC. The results were that the AEC at doses of 40mg/kg/d, 80mg/kg/d and 160 mg/kg/d possessed evident antifertility effects on mice. Their fertility inhibition ratio were 72.2%、88.2% and 90%(compared with control, p<0.01), respectively, the amount of foetus were reduced apparently. In addition, the fertility inhibition effect was found dose dependent as increase in concentration. The implantation ratio at doses of 40mg/kg/d、80mg/kg/d and 160 mg/kg/d were 3/8、1/6 and 1/6; The ratio of pregnancy at the dose of 40 mg/kg/d was reduced apparently. There were almost no changes in the index of ovary, spleen and drenal gland in the mice treated with AEC, but the index of thymus was increased at the dose of 40 mg/kg/d, moreover, the increase of the index of thymus was dose-dependent(p<0.01).
2 Kunming mice were gavaged AEC at doses of 0mg/kg/d, 20mg/kg/d, 40mg/kg/d, 80mg/kg/d and 160 mg/kg/d for one week respectively. In order to investigate the antifertility mechanism of AEC, the mice were taken to study the sexual cycle, pregnancy-associated plasma protein A(PAPP-A) and the level of sexual hormone such as estradiol(E2) and progesterone(P), as well as the microstructure of ovaries, fallopian tube and uterus after the administration. The results were that the sexual cycles of mice treaded with 40mg/kg/d, 80mg/kg/d and 160 mg/kg/d were changed, mainly diestrus was erratically extended. From the 20 mg/kg/d, the PAPP-A of the treaded mice was lower than that of control, and from 40 mg/kg/d the decrease of PAPP-A was evident. There were no notable changes in the E2 level of treated mice, but the P level was increased in a certain extent. The 77.78% un-pregnant uteri suffused with colorless transparent fluid treated at a dose of 40mg/kg/d was evidently inflated. Histological observation showed that the height of epithelium in AEC treated un-pregnant uteri was significantly increased, and that the thickness of endometrium stromal layer, in which the glands were fewer and the muscle layer of which the cells ranged irregularly, was decreased.
3 The morphology and the viability of the cells being taken as an index, the direct effects of AEC on the primary cultured rat decidual stormal cells(DSC) and rat luteal cells were observed. The results indicated that: AEC has inhibitory effects on rat decidual stomal cells(DSC) at a dose of 400μg/mL(P<0.05). In addition, the depressant effect was found dose dependent as increase in concentration increased the inhibition. When the concentration reached 80μg/mL, many DSC died(P~-0.001). The IC_(50) of AEC on DSC was 568.6±5.3μMg/mL, r=+0.9790. But AEC has no inhibiting effects on rat luteal cells. The results suggested that the test on the viability of cultured rat decidual stormal cells could be used as a guide of bioassay-guided separation and isolation of AEC contraceptive activity components.
4 AEC, which possessed antifertility activity and contraceptive efficacy in female rodents, were evaluated for their in vitro inhibitory activity in the primary cultured rat decidual stromal cells(DSC). A bioassay-guided fractionation technique was used to separate active components from crude extracts. A colorless crystal showed a significant inhibitory activity(IC_(50)=63.84±3.04μg/mL, r=+0.9478). The chemical analysis of the colorless crystal by capillary gas chromatography-mass spectrometry(GC-MS) revealed that the colorless crystal was a mixture of five components: four phytosterols which were ergost-5-en-3-ol(6.10%), stigmasterol(35.80%),γ-sitosterol(44.77%) and fucosterol(8.40%); and one probucol analog(4.93%). It was presumed thatγ-sitosterol may be the main component contributing to inhibit the viability of DSC, and the stigmasterol might act as an assistant.
有关不育对鼠类种群繁殖力和数量影响的研究表明：不育能够取得灭杀的效果，若考虑不育的干扰作用，不育方法比灭杀更能控制鼠类种群数量的增加；不育控制鼠害的实验表明，雌性不育比雄性不育效果好，而双性不育比单性不育效果更好。在近年来兴起的植物不育剂的研究和开发中，许多植物源不育剂是针对抗雄鼠生育的，而抗雌鼠生育植物不育剂的研究和开发却较少见。其主要原因是在雌性不育剂有效成分的研发过程中，作为导向分离的筛选靶标较难确定，造成筛选抗雌鼠生育有效成分难度比较大。
蓖麻油是大戟科植物蓖麻(Ricinus communis L．)种子的乙醚提取物(AEC)。在我国传统医学中，蓖麻油具有泻下通滞、消除痈疽肿毒、导泻等功能；临床上用蓖麻油抄鸡蛋进行催产已有多年的历史；在印度、朝鲜、约旦等国和一些非洲国家，妇女常常服用蓖麻籽及其提取物来进行避孕。有研究表明，蓖麻油具有抗雌鼠和雄鼠生育的作用，且其抗生育活性较强。为了研制新型的鼠类不育剂，本研究对蓖麻油抗雌鼠生育作用和作用机理进行了研究，建立了抗雌鼠生育活性物质的体外筛选方法，导向分离出具有较强抗雌鼠生育活性的晶体物质，并对这一抗雌鼠生育活性晶体物质进行了分析。本论文研究的结果既为开发高效、安全的植物源抗鼠生育药物提供有效药源，又为我国蓖麻资源的综合利用开辟了新途径，有利于提高蓖麻产业经济效益与社会效益；有利于为创制与环境相容的高效植物源生物鼠不育剂、开发出具有我国自主知识产权的新型植物源农药，奠定坚实的理论基础。本论文主要研究内容和结果如下：
1、通过用蓖麻油在特定的时间内连续灌胃小鼠，统计怀孕率和胚胎数量，研究蓖麻油的抗早孕、抗着床作用。结果表明：20 mg/kg/d处理组小鼠受孕率降低不明显，但是小鼠所孕胎儿总数有一定的减少；40 mg/kg/d及其以上浓度的两个处理浓度小鼠受孕率明显降低，其生育抑制率分别达到：72.2％、88.2％和90％(与对照组比较，p<0.01)，个体所孕的胎儿数也明显减少；蓖麻油对小鼠的生育抑制作用有一定的量-效关系；在抗着床方面，40 mg/kg/d、80 mg/kg/d和160 mg/kg/d三个处理组的子宫内着床位点明显减少，着床率明显降低，分别为：3/8、1/6和1/6；在抗早孕方面，从40 mg/kg/d处理浓度开始，小鼠怀孕率明显降低，生育抑制率显著提高；小鼠怀孕的胎儿数随着处理浓度的增加而减少；此外，蓖麻油处理组卵巢和免疫系统主要的器官脾和肾上腺指数变化不明显，但从40 mg/kg/d处理浓度开始，小鼠胸腺增大、胸腺指数增加。随着处理浓度的加大，胸腺指数增加得越显著(p<0.01)。
2、采用灌胃蓖麻油后对小鼠动情周期、血清雌二醇(E2)、孕酮(P)等性激素水平和妊娠相关蛋白-A(pregnancy-associated plasma protein A，PAPP-A)变化情况，以及蓖麻油引起的未怀孕体质健壮小鼠的卵巢、输卵管和子宫结构变化进行研究，探讨蓖麻油抗生育活性的作用机理。结果表明：20mg/kg/d剂量蓖麻油处理组小鼠动情期的时间和表现与对照组比较均无明显区别；而40mg/kg/d及其以上处理组小鼠在动情期生理特征不明显，动情期缩短，动情间期延长且不规则。小鼠血清中的雌二醇(E2)水平无明显变化，而孕酮(P)含量有一定的升高；在20 mg/kg/d处理组，小鼠血浆中的PAPP-A稍微低于对照组；而从40 mg/kg/d处理剂量开始，PAPP-A值降低显著；且随着蓖麻油处理浓度的增加，PAPP-A值降低程度增大；蓖麻油40 mg/kg/d剂量处理组和以上浓度剂量处理组膨大子宫与正常对照未孕雌鼠子宫相比，其内腔扩大，子宫壁明显变薄；肌肉层比对照组薄，肌纤维排列疏松、紊乱：子宫基质层变薄，其内腺体减少；黏膜上皮增厚。
3、通过用不同剂量蓖麻油处理原代培养大鼠蜕膜细胞和黄体细胞，观察细胞形态变化，同时用MTT法检测细胞活力，确定了蓖麻油抗雌鼠生育活性成分的作用靶标，首次建立蓖麻油抗生育有效成分的体外筛选方法。结果表明：400μg/mL及其以上浓度蓖麻油处理液对体外培养大鼠蜕膜细胞形态有明显的影响，400μg/mL蓖麻油处理液使部分离体培养蜕膜细胞体积比正常细胞明显减小、细胞内出现明显空泡，部分细胞胞浆皱缩、死亡。MTT法检测发现：400μg/mL及其以上处理浓度的蓖麻油对蜕膜细胞的生长有显著的抑制作用(p<0.05)；蓖麻油对蜕膜细胞的半抑制浓度(IC_(50))为568.6±5.3μg/mL，r=+0.9790；且这一抑制作用具有良好的量-效关系。而蓖麻油对黄体细胞活力的抑制作用不显著，仅仅表现在600μg/mL浓度蓖麻油处理24h的大鼠黄体细胞体积变小，细胞数量略有减少。用大鼠离体培养蜕膜细胞的活力测定方法作为蓖麻油抗雌鼠生育有效成分分离、提纯的活性跟踪指标是可行的。
4、以原代培养大鼠蜕膜细胞(DSC)活力作为筛选靶标，首次导向分离蓖麻油(AEC)中的抗生育活性成分。经过皂化、乙醚萃取、乙醇重结晶和活力检测等步骤，获得一种对大鼠蜕膜细胞活力有抑制作用的无色晶体，其半抑制浓度(IC_(50))为63.84±3.04μg/mL，r=+0.9478。GC-MS分析和计算机相似性比较表明：无色晶体由5种成分组成，其中有4种成分为植物甾醇。5种成分分别是：麦角甾-5-稀-3-醇(Ergost-5-en-3-ol)，豆甾醇(Stigmasterol)，v-谷甾醇(γ-Sitosterol)、岩藻甾醇(Fucosterol)，和普罗布考(Probucol)类似物等。其中γ-谷甾醇(7-Sitosterol)的含量最高，达44.77％；其余组分的含量分别是：豆甾醇(Stigmasterol)占35.80％，岩藻甾醇(Fucosterol)占8.40％，麦角甾-5-稀-3-醇(Ergost-5-en-3-ol)占6.10％和普罗布考(Probucol)类似物占4.93％。根据实验结果和文献报道推测：γ-谷甾醇(7-Sitosterol)很有可能是抑制离体培养大鼠蜕膜细胞活力的主要成分；而豆甾醇(stigmasterol)可能起协助的作用。
Rodent pest is a worldwide calamity, which is one of leading disasters in the field of bio-agriculture. In China, tremendous economic losses in the fields of agriculture, forestry and animal husbandry are caused by Rodent pests. The effective control of rodents is of importance to ensure the agriculture sustainable development. Presently, the mainly rodents control method in the world is chemical control, most of the rodenticides mainly cause the increase of the mortality of mice and could not keep long effect, the low density of mice can maintain only one year, since the density of mice rise gradually and restore to the previous level. In addition, chemical rodenticides possess the side-effects on environment and living things. Due to the shortcomings of traditional rodenticides, the new rodenticide is urgently necessary for the efficacious and continuous reduction of mice: the population density of mice could be reduced by decreasing the reproduction rate of mice, namely, developing a new strategy of biological sterilization of rodents.
The results of the investigation on the effect of sterility on the rodent reproduction and their population demonstrated that: Decreasing the reproductive ratio instead of increasing mortality had been suggested as a promising means for managing the impact of overabundant species. Sterilized resident females were thought to restrict reproduction on the population level if they maintained their territories and social status and prevented subordinates from breeding. Many botanic sterilants development in recently years acted on male rodents, but few acted on female. The reason was that the choice of guide for bioassay-guided fractionation of antifertility components in female rodents was difficult.
Castorbean oil, an aether extract from the castorbean seeds(Ricinus communis L.)(AEC), has been known to possess medicinal property of antifertility activity on both female and male mammals. In order to developing new sterilants, the antifertility effect and the machinsm of castorbean oil in female rodents were investigated, the in vitro method for separating the contraceptive components of AEC was established; a colorless crystal which showed a significant inhibitory activity on rat decidual stormal cells was separated by means of bioassay-guided fractionation, and the colorless crystal was chemically analyzed. The results of the research not only supplied high-effective and safe botanic medicine for antifertility of rodents, but also established a new way of comprehensive utilization of castorbean resource of our country, which was beneficial to developing castorbean industry. It will helpful to the establishment of the substantial rationale for the developing of high-effective botanic antifertility medicine of our country possessing independent intellectual property rights, and also for the developing of the neotype botanic rodentcide. The main results are showed as follows.
1 Kunming mice were gavaged the AEC at doses of 0mg/kg/d, 20mg/kg/d, 40mg/kg/d, 80mg/kg/d and 160 mg/kg/d in specified time respectively. The amount of pregnancy mice and the embryos were added up for the research on the anti-early pregnancy and anti-implantation of AEC. The results were that the AEC at doses of 40mg/kg/d, 80mg/kg/d and 160 mg/kg/d possessed evident antifertility effects on mice. Their fertility inhibition ratio were 72.2%、88.2% and 90%(compared with control, p<0.01), respectively, the amount of foetus were reduced apparently. In addition, the fertility inhibition effect was found dose dependent as increase in concentration. The implantation ratio at doses of 40mg/kg/d、80mg/kg/d and 160 mg/kg/d were 3/8、1/6 and 1/6; The ratio of pregnancy at the dose of 40 mg/kg/d was reduced apparently. There were almost no changes in the index of ovary, spleen and drenal gland in the mice treated with AEC, but the index of thymus was increased at the dose of 40 mg/kg/d, moreover, the increase of the index of thymus was dose-dependent(p<0.01).
2 Kunming mice were gavaged AEC at doses of 0mg/kg/d, 20mg/kg/d, 40mg/kg/d, 80mg/kg/d and 160 mg/kg/d for one week respectively. In order to investigate the antifertility mechanism of AEC, the mice were taken to study the sexual cycle, pregnancy-associated plasma protein A(PAPP-A) and the level of sexual hormone such as estradiol(E2) and progesterone(P), as well as the microstructure of ovaries, fallopian tube and uterus after the administration. The results were that the sexual cycles of mice treaded with 40mg/kg/d, 80mg/kg/d and 160 mg/kg/d were changed, mainly diestrus was erratically extended. From the 20 mg/kg/d, the PAPP-A of the treaded mice was lower than that of control, and from 40 mg/kg/d the decrease of PAPP-A was evident. There were no notable changes in the E2 level of treated mice, but the P level was increased in a certain extent. The 77.78% un-pregnant uteri suffused with colorless transparent fluid treated at a dose of 40mg/kg/d was evidently inflated. Histological observation showed that the height of epithelium in AEC treated un-pregnant uteri was significantly increased, and that the thickness of endometrium stromal layer, in which the glands were fewer and the muscle layer of which the cells ranged irregularly, was decreased.
3 The morphology and the viability of the cells being taken as an index, the direct effects of AEC on the primary cultured rat decidual stormal cells(DSC) and rat luteal cells were observed. The results indicated that: AEC has inhibitory effects on rat decidual stomal cells(DSC) at a dose of 400μg/mL(P<0.05). In addition, the depressant effect was found dose dependent as increase in concentration increased the inhibition. When the concentration reached 80μg/mL, many DSC died(P~-0.001). The IC_(50) of AEC on DSC was 568.6±5.3μMg/mL, r=+0.9790. But AEC has no inhibiting effects on rat luteal cells. The results suggested that the test on the viability of cultured rat decidual stormal cells could be used as a guide of bioassay-guided separation and isolation of AEC contraceptive activity components.
4 AEC, which possessed antifertility activity and contraceptive efficacy in female rodents, were evaluated for their in vitro inhibitory activity in the primary cultured rat decidual stromal cells(DSC). A bioassay-guided fractionation technique was used to separate active components from crude extracts. A colorless crystal showed a significant inhibitory activity(IC_(50)=63.84±3.04μg/mL, r=+0.9478). The chemical analysis of the colorless crystal by capillary gas chromatography-mass spectrometry(GC-MS) revealed that the colorless crystal was a mixture of five components: four phytosterols which were ergost-5-en-3-ol(6.10%), stigmasterol(35.80%),γ-sitosterol(44.77%) and fucosterol(8.40%); and one probucol analog(4.93%). It was presumed thatγ-sitosterol may be the main component contributing to inhibit the viability of DSC, and the stigmasterol might act as an assistant.
引文
[1]中华人民共和国药典编辑委员会，中华人民共和国药典(1995年版)，广东科学技术出版社，广州，pp.312-313．
[2]马玲．蓖麻餐在晚期妊娠引产中的应用．中华临床医药，2003，3(2)：21．
[3]杨宗梅．蓖麻油 米索前列醇用于足月引产临床比较．医药论坛杂志，2003，24(6)：62．
[4]Salhab AS, Shomaf MS, Gharaibeh MN, Amer NA. Effects of Castor Bean Extract and Ricin A-Chain on Ovulation and Implantation in Rabbits. Contraception,1999,59∶395-399.
[5]Abdulazim S. Salhab, Salah O. A1-Tamimi，Munir N. Gharaibehand Maha，et al. The Abortifacient Effects of Castor Bean Extract and Ricin-A Chain in Rabbits. Contraception，1998，58:193-197.
[6]ZHANG Chun-mei, WANG Rui-hong.Advance in the research of sterilants against rodents. Journal of Forestry Research, 2002，13(1): 77-81.
[7]Okwuasaba FK, Osunkwo UA, Ekwenchi MM, et al. Anticonceptive and estrogenic effects of a seed extract of Ricinus var. minor. Journal of Ethnopharmacology,1991, 34(2)∶141-145.
[8]Isichei CO, Das SC, Ogunkeye OO, Okwuasaba FK, Uguru VE, Onoruvwe O, Olayinka AO, Dafur SJ, Ekwere EO, Parry O. Preliminary Clinical Investigation of the Contraceptive Efficacy and Chemical Pathological Effects of RICOM-1013-J of Ricinus communis var Minor on Women Volunteers. Phytothearapy Research, 2000,14. 40-42.
[9]左风．蓖麻籽抗生育作用的毒理及临床研究．国外医学中医中药册，2901,23(5)∶286-287．
[10]Scarpa A, Guerci A. Various uses of the castor oil plant Ricinus communis. A review. JEthnopharmacol, 1982, 5∶117-137.
[11]Malhi BS，Trivedi VP. Vegetable antifertility drugs of India. Q J Crude Drug Res,1972, 12:1922-1928.
[12]Woo WS, Lee EB, Shin KH, Kang SS, Chin HJ.A review of research on plants for fertility regulation in Korea. Kor J Pharmacogn, 1981, 12∶153-70.
[13]Brondegaard VJ. Contraceptive plant drugs. Planta Med，1973，23∶167-71.
[14]Salhab AS, Issa A, Alhougog I.On the contraceptive effect of castor beans. Int J Pharmacogn 1997，35∶63-65.
[15]Das SC, Isichei CO，Okwuasaba FK，Uguru VE，Onoruvwe O，Olayinka AO，Ekwere E O, Dafur SJ, Parry O. Chemical, Pathological and Toxicological Studies of the Effects of RICOM-1013-J of Ricinus communis var Minor on Women Volunteers and Rodents. Phytothearapy Research，2000，14，15-19.
[16]Sandhyakumary K, Bobby RG and Indira M. Antifertility Effects of Ricinus communis (Linn)on Rats. Phytothearapy Research，2003，17，508-511.
[17]Okwuasaba FK, Das SC, Isichei CO, Ekwenchi MM, Onoruvwe O, Olayinka AO，Uguru VE，Dafur SJ，Ekwere EO, Parry O, The Anticonceptive and the effect on uterus of ether extract 18312-J of Ricinus communis. Phytothearapy Research，1997(a)，10，97-100.
[18]Okwuasaba FK, Das SC, Isichei CO, Ekwenchi MM, Onoruvwe O, Olayinka AO，Uguru VE, Dafur SJ，Ekwereand EO，Parry O. Pharmacological Studies on the Antifertility Effects of RICOM-1O13-J from Ricinus communis var minor and Preliminary Clinical Studies on Women Volunteers. Phytothearapy Research，1997，11，547-551.
[19]张知彬．鼠类不育控制的生态学基础．兽类学报，1995a，15(3)∶229-234．
[20]张知彬．鼠类种群数量的波动与调节．王祖望，张知彬主编．鼠害治理的理论与实践．北京：科学出版社．1996a，pp145-165．
[21]张知彬．我国草原鼠害的严重性及防治对策．中国科学院院刊，2003，(5)∶434-437．
[22]秦晓娜，高平，甘明哲．蓖麻提取物对鼠抗生育作用研究，四川动物，2006，25(1)∶176-179．
[23]吴小丽，蔡云清，赵岩，李世芬．蒲公英提取物对小鼠免疫功能的调节作用．南京医科大学学报(自然科学版)，2005，25(3)∶163-165．
[1]中华人民共和国药典编辑委员会，中华人民共和国药典(1995年版)，广东科学技术出版社，广州，pp.312-313．
[2]马玲．蓖麻餐在晚期妊娠引产中的应用．中华临床医药，2003，3(2)∶21．
[3]Malhi BS, Trivedi VP.Vegetable antifertility drugs of India. Q J Crude Drug Res,1972, 12: 1922-1928.
[4]Woo WS, Lee EB, Shin KH, Kang SS, Chin HJ. A review of research on plants for fertility regulation in Korea. Kor J Pharmacogn, 1981,12∶153-70.
[5]Okwuasaba FK, Das SC, Isichei CO，Ekwenchi M M, Onoruvwe O, Olayinka AO, Uguru VE,Dafur SJ, Ekwere EO and Parry O. The Anticonceptive and the Effect on Uterus of Ether Extract, 18312-J of Ricinus communis, Phytotherapy Research, 1997a,10, 97-100.
[6]Okwuasaba FK, Das SC, Isichei CO, Ekwenchi MM, Onoruvwe O, Olayinka AO, Uguru VE, Dafur SJ, Ekwereand EO, Parry O. Pharmacological Studies on the Antifertility Effects of RICOM-1013-J from Ricinus communis var minor and Preliminary Clinical Studies on Women Volunteers. Phytotheapy Reearch, 1997b, 11,547-551.
[7]Isichei CO, Das SC, Ogunkeye OO, Okwuasaba FK, Uguru V E, Onoruvwe O,Olayinka AO, Dafur SJ, Ekwere EO and Parry O. Preliminary Clinical Investigation of the Contraceptive Efficacy and Chemical Pathological Effects of RICOM-1013-J of Ricinus communis var Minor on Women Volunteers. Phytotheapy Reearch 2000, 14, 40-42.
[8]Das SC, Isichei CO, Okwuasaba FK, Uguru VE, Onoruvwe O, Olayinka AO, Ekwere EO, Dafur SJ and Parry O. Chemical, Pathological and Toxicological Studies of the Effects of RICOM-1013-J of Ricinus communis var Minor on Women Volunteers and Rodents. Phytotheapy Reearch, 2000, 14, 15-19.
[9]秦晓娜，高平，甘明哲。蓖麻提取物对鼠抗生育作用研究，四川动物，2006，25(1)∶176-179。
[10]Arici A, Matalliotakis I, Goumenou A, et al. Increased pregnancy-associated plasma protein-a(PAPP-A)concentrations in peritoneal fluid of women with endometriosis. Am J Reprod Immunol. 2003, 49(2)∶70-74.
[11]董源芬，宋扬。应用时间分辨荧光法测定妊娠相关血浆蛋白A的临床意义。中国优生与遗传杂志，2005，13(12)：55-56．
[12]刘蓓，章晓梅，邓莲。妊娠相关血浆蛋白A在辅助生殖医学中的研究进展国外医学计划生育(生殖健康分册)，2006，25(5)：260-263．
[13]张春美，陈荣，周维民．我国鼠类抗生育药剂的研究进展．Forest pest and Disease，2001，1∶34-35．
[14]方琳丽，王鲁华，奚宝珊．女性不孕症患者血清性激素水平的变化．放射免疫学杂志，2001,13(5)∶298．
[15]邓莲，章晓梅，李春华，李永刚 马艳萍，高梦莹，冯怀瑛。妊娠相关血浆蛋白-A与人绒毛膜促性腺激素在卵泡发育中的关系，生殖医学杂志，2005，14(5)∶280-283．
[16]杨文秀．苯乙烯对生殖内分泌和动情周期的影响．癌变.畸变．突变，1995，(6)∶358-360．
[17]李美芝主编．妇科内分泌学[M]．北京：人民军医出版社．2001，4．
[18]于学文，高成阁，金辉．雌激素的抗抑郁作用．中华妇产科杂志，2003，38(2)∶113－114．
[19]Hofbauer LC, Khosla S, Dunstan CR, et al. Estrogen stimulates gene expression and protein production of osteopmtegerin in human osteoblastic cells. Endocrinology, 1999,140∶4367-4370.
[20]米芳芳．雌激素生物作用的研究．中医药研究，2001，18(2)：48-49．
[21]陈志龙，1984，子宫内膜组织病理学．
[22]郑光，周志俊一，载旭峰，孙运光，郑捷，唐颖，孙毅．小鼠子宫增重试验检测六种常用有机磷农药拟雌激素样活性．Carcinogenesis，Teratogenesis and Mutagenesis．2004,16(4)：211-231．
[1]Okwuasaba FK, Das SC, Isichei CO, et al. The Anticonceptive and the Effect on Uterus of Ether Extract 18312-J of Ricinus communis. Phytother Res, 1997a, 10∶97-100.
[2]Okwuasaba FK, Das SC, Isichei CO, et al. Pharmacological Studies on the Antifertility Effects of RICOM-1013-J from Ricinus communis var minor and Preliminary Clinical Studies on Women Volunteers. Phytother Res, 1997b, 11:547-551.
[3]Das SC, Isichei CO, Okwuasaba FK, et al. Chemical, pathological and toxicological studies of the effects of RICOM-1013-J of Ricinus communis var minor on women volunteers and rodents. Phytother Res, 2000, 14∶15-19.
[4]Isichei CO, Das SC, Ogunkeye OO, et al. Preliminary clinical investigation of the contraceptive efficacy and chemical pathological effects of RICOM-1013-J of Ricinus comrnunis var minor on women volunteers. Phytother Res, 2000, 14:40-42.
[5]秦晓娜，高平，甘明哲．蓖麻提取物对鼠抗生育作用研究．四川动物，2006，25(1)∶176-179．
[6]陈浩宏，顾芝萍，游根娣，庄临之．人蜕膜细胞培养作为抗早孕药物筛选模型的研究．上海铁道大学学报，1998，19(11)∶1-3．
[7]张曙萱，王海琦，欧宁。马鞭草提取液对体外培养人早孕蜕膜细胞的影响。中国天然药物，2004，2(4)∶242-246．
[8]Okwuasaba, FK, Osunkwo, UA, and Ekwenchi, MM. et al. Anticonceptive and estrogenic effects of a seed extract of Ricinus communis var minor.J.Ethnopharmacol. 1991, 34, 141-145.
[9]程宝鸾等编。动物细胞培养技术，华南理工大学出版社，广州，2003，8．第一版，pp131-132．
[10]Carmichael J, William GD, Adi FG, et al. Evealuation of a tetrazolium-based semiautiomated colorimetric assay:assessment of chemosensitivity testing. Cancer Res, 1987, 47∶936.
[11]刘承权．抗着床抗早孕药物的药效学研究进展．中国药学杂志，1988，8(3)∶72－75．
[12]Wynn RM．子宫生物学．北京：人民卫生出版社，1980：pp214-215．
[13]冷颖，杨纫姝．钙调素拮抗剂对离体培养人蜕膜细胞形态和活力的影响．生殖与避孕，1997，17(2)∶76～81．
[1]中华人民共和国药典编辑委员会，中华人民共和国药典(1995年版)，广东科学技术出版社，广州，pp．312-313．
[2]王慧．口服蓖麻油煎鸡蛋能缩短产程．中国民间疗法，2000，8(12)∶46．
[3]潘丽，张瑞玲。妊娠晚期用蓖麻油引产餐引产的临床研究。中华现代临床医学杂志，2005,3(3)∶269-270．
[4]Okwuasaba FK，Das SC, Isichei CO, Ekwenchi MM, Onoruvwe O, Olayinka AO, Uguru VE, Dafur SJ, Ekwere EO, Parry O. The Anticonceptive and the effect on uterus of ether extract 18312-J of Ricinus communis. Phytotherapy Research 1997 (a), 10, 97-100.
[5]Okwuasaba FK, Das SC, Isichei CO, Ekwenchi MM, Onoruvwe O, Olayinka AO, Uguru VE, Dafur SJ, Ekwere EO, Parry O. Pharmacological studies on the antifertility effects of RICOM-1013-J from Ricinus communis var minor and preliminary clinical studies on women volunteers. Phytotherapy Research, 1997(b)，11，547-551.
[6]Isichei CO, Das SC, Ogunkeye OO, Okwuasaba FK, Uguru VE, Onoruvwe O, Olayinka AO, Dafur SJ, Ekwere EO, Parry O. Preliminary clinical investigation of the contraceptive efficacy and chemical pathological effects of RICOM-1013-J of Ricinus comrnunis var minor on women volunteers. Phytotherapy Research, 2000,14, 40-42.
[7]Das SC, Isichei CO, Okwuasaba FK, Uguru VE, Onoruvwe O, Olayinka AO, Ekwere EO, Dafur SJ, Parry O. Chemical, pathological and toxicological studies of the effects of RICOM-1013-J of Ricinus communis var minor on women volunteers and rodents. Phytotherapy Research, 2000, 14, 15-19.
[8]Sandhyakumary K, Bobby RG, Indira M. Antifertilit effects of Ricinus communis(Linn) on Rats. Phytotherapy Research, 2003,17, 508-511.
[9]秦晓娜，高平，甘明哲．蓖麻提取物对鼠抗生育作用研究．四川动物，2006，25(1)∶176-179．
[10]陈浩宏，顾芝萍，游根娣，庄临之．人蜕膜细胞培养作为抗旱孕药物筛选模型的研究．上海铁道大学学报，1998，19(11)∶1-3．
[11]Carmichael J, William GD, Adi FG，John DM, James BM, Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing. Cancer Research, 1987, 47∶936.
[12]陈萌．蓖麻籽油的成份分析．云南化工，1998，(2)：46-47．
[13] Mellanen, P, Petanen, T, Lehtimaki, J, Makela, S, Bylund，G，Holmbom, B, Mannila, E, Oikari, A, Santti, R. Woodderived estrogens: Studies in vitro with breast cancer cell lines and in vivo in trout. Toxicol. Appl. Pharmacol. 1996, 136, 381-388.
[14]Ethan DC, Alison CR. Behavioral changes in fish exposed to phytoestrogens Environmental Pollution. 2006,144, 833-839.
[15]Tarja N, Kirsti E. Effects of phytosterols on zebrafish reproduction in multigeneration test. Environmental Pollution, 2003,123, 267-273.
[16]Khan MR, Mlungwana SM. γ-Sitosterol, a cytotoxic sterol from Markhamia zanzibarica and Kigelia Africana. Fitoterapia, 1999, 70:96-97.
[17]高瑜莹，裘爱泳，谢光，陈宗杰．溶剂法富集豆甾醇的研究．中国油脂，2000，25(6)：159-162．
[18]许文林，王雅琼，鲁萍．脱臭馏出物中植物甾醇的回收和精制．过程工程学报，2002a，2(2)：167-170．
[19]许文林，王雅琼，黄一波，鲁萍．重结晶法精制植物甾醇的溶剂选择．扬州大学学报(自然科学版)，2002(b)：5(1)：58-61,70．
[1]王祖望，张自彬．害鼠治理的理论与实践[M]．北京：科学出版社．1996，pp344-366．
[2]李翰，徐守成．大通县森林病虫害发生趋势预测及防治策略．青海农林科技，1999，(3)：28-30．
[3]邓址．啮齿动物的生态与防治[M]．北京：北京师范大学出版社．1989，pp13-18．
[4]韩崇选，王明春，杨学军．安全型无公害灭鼠剂—克鼠星的研制．西北林学院学报，2002，17(3)：44-47．
[5]周梅花，马有国．平面直方图在森林病虫害防治中的应用．青海农林科技，1999，(1)：35-37．
[6]张知彬．我国草原鼠害的严重性及防治对策．中国科学院院刊，2003，(5)∶434-437．
[7]杨学军，韩崇选，王明春，张宏利，杨清娥，李继光，何燕．林区鼠害的无公害治理与生态环境保护对策．2003，95(3)∶54-57．
[8]赵树芹．谈天然林鼠害及其防治．黑龙江林业，2003,6∶27．
[9]张宏利，卜书海，韩崇选，杨学军，王明春，杨清娥，吕宁．鼠害及其防治方法研究进展．西北农林科技大学学报(自然科学版)，2003，31(增刊)：167-172．
[10]王廷正，李金钢，张越，等．黄土高原啮齿动物区系及鼢鼠成因分析[M]．黄土高原林区鼢鼠综合管理研究[M]．西安：西北大学出版社，1995．pp1-11．
[11]王明春，韩崇选，杨学军．克鼠星1号防治甘肃鼢鼠研究．西北林学院学报，1999，14(2)：51-56。
[12]韩崇选，杨学军，王明春．多效抗旱驱鼠剂的苗木处理方法与效果．西北林学院学报，2001，16(4)：41-45．
[13]许毅达．在西部地区推广“绿色灭鼠工程”．学会月刊，2002，11：28-29．
[14]夏瑞心，巩向日．我国森林鼠害防治对策．辽宁林业科技，1997，(6)：47-51．
[15]李忠杰．C肉毒杀鼠素干冻剂防治草原鼠害试验初报．宁夏农林科技，1998，(1)：30．
[16]王贵林，沈世英．C型肉毒梭菌毒素杀灭高原鼢鼠的初步研究．兽类学报，1988，8(1)：76-77．
[17]汪志刚，杨心茂，周俗．C型肉毒梭菌毒素灭鼠新技术示范推广初报．四川草原，1990，(3)：47-49,58．
[18]王振飞，次仁罗布．C肉毒梭菌毒素灭鼠试验．西藏畜牧兽医，1991，(4)：23-25．
[19]Knipling EF.Sterile male method of population control.Sci.1959，130-902.
[20]Davis DE. Principles for populationaontrolby gametocides. Tram.N.Am. Wildl.Conf, 1961,26:160
[21]Howard WE. Biocontrol and chemosterilants. In Pestcontrol: Biological, Physical and Selected Chemical Methods (Eds.)W W. Kilgore & R L doutt Academic Press, New York and London, 1967. pp343-386.
[22]高源.鼠类化学不育剂的发展.中国媒介生物学及控制杂志，1996, 7(6): 481-484.
[23]Caughley, G, Pech R. and Grice D. Effect of fertility control on a population’s productivity. Wildlife Research. 1992, 19: 623-627.
[24]张知彬．鼠类不育控制的生态学基础．兽类学报，1995a，15(3)：229-234．
[25]张知彬．免疫不育在动物数量控制上的应用前景．医学动物防制，1995b，11(2)： 194-197．
[26]张知彬．鼠类种群数量的波动与调节．王祖望，张知彬主编．鼠害治理的理论与实践．北京：科学出版社．1996a，pp145-165．
[27]Chamber, LK, Singleton GR and Hinds LA. Fertility control of wild mouse populations: the effects of hormonal competence and animposed level of sterility. Wildlife Research, 1999a, 26:579-591.
[28]Chambers, LK, Lawson MA and Hinds LA. Biological control of rodents the case for fertility control using immunocontr-ception. In∶Singleton, G. R., L. A. Hinds, H. Leris and Z. B. Zhang ed. Ecologically-based Rodent Management. A CIAR Monograph. 1999b, 59: 215-242.
[29]Marsh RE & Howard W E Prospects of Chemosterilant genetic control of rodents. Bull Wild Hlth Org. 1973,48: 309.
[30]Marsh RE. Chemo-sterilants for rodent control. In Rodent Pest Management (Ed.) I.Prakash, CRC Press, Florida.1988, 353-367.
[31]Ericsaon RJ. Alphechlorohydrin (Epiblocr): a toxicant sterilant as an alternative in rodent control.Proc.10ch Vet. Pest Conf. Monterty, Calif, 1982, 5-9.
[32]朱靖，张知彬．农牧业鼠害综合治理的研究现状及对策．农牧业情报研究，1988，7∶1-10．
[33]Meehan AP. Rats and Mice, Their Biology and Control.Rentokil Liruited, Susser, 1984.
[34]Griffith W. Epibloc rodenticide introduces a new concept in”long-term”rodent control. Pest Control Tachnol. 1983,11 (4):42,64,67.
[35]Ericaacon RJ. Male antifertility compounds: U-5897 as a rat chemosterilant, J Reprod. Fert., 1970, 22:213.
[36]Jones AR. The antifertility actions of a-chlorohydrin in the male.Life Sci, 1978, 25:1625.
[37]Andrews RV, Belknap RW. Efficacy of a-chlorohydrin in sewer rat control. J.Hyg, Canto, 1983, 91:359.
[38]Ericsson RJ. Alphachlorohydrin (Epibloc): a toxicant sterilant as an alternative in rodent.control. Proc. of Tenth Vertebrate Pest Conference (R. E. Marshed.). 1982, 6-9.
[39]Handel DJ. In: Pharmacology, Biology, and clinical application of an-drogens, Current status and future prospects,Proceedings for the Second International Androgen Workshop.Califomia:Wiey-Liss, 1996,395-407.
[40]Gao Y, Short RV. Use of an oestrogen, androgen or gestagen as a potential chemosterilant for control of rat and mouse population, J Rrprod.Fer,1993, 97:392.
[41]Jackson H. Antifertility substances.Pharmacol.Rev,1959.11:135.
[42]Meriggiola MC, Bremner WJ, Paulsen CA, et al. A combined regimen of cyproterone acetate and testerone enanthate as a potentially highly effective male contraceptive.J Clin Endocrinol Metab, 1996, 81:3018-3023.
[43]Gao Y, Short RV. Fertility control in wild mice after feeding with RU486 or methyl testosterone.J.Reprod.Fert, 1994,101:483.
[44]Benhamou B. A single amino acid that determines sensitivity of progesterone receptors to RU486, Science, 1992, 255:206
[45]Swerdloff RS, Bagatell CJ, Wang C, et al. Suppression of spermatogenesis in man induced by Nal-Glu gonadotropin releasing hormone antagonistand testosterone enanthate (TE) is maintained by TE alone.J Clin Endocrinol Metab, 1998, 83 (10):3527-3533
[46]张春美，陈荣，周维民．我国鼠类抗生育药剂的研究进展．中国森林病虫，2001(1)：34-35．
[47]Miller SE，Chamow SM，Baur AW，Liver C，Robery F，Dean J．Vaccination with a synthetic zona pellucida peptide produces long-term contraception in female mice．Science，1989，246：935-938．
[48]Miller LA．Comparative effiency of two immuno-contraceptive vaccines for controuing wild Norway rats(Abstract)．P6，1993 Symposium on Contraception in Wildlife Management Oct．Denver Colorado．26-28．
[49]Shaha C，Kaul S，Kini M，Chaudhury M，Anad R，Das C and Talwar GP．Immunization against LHRH without the use of Freud’s complete adjuvant．1986， p143-150. Immunological Approaches to Contraception and Promotation of Fertility (G.P. Talwar ed). Plenum Press, New York.
[50]Thompaon RD, Miller LA and Johns BE. White-tailed deer immuno-contraception using porcine zona pellucida and recombinant rabbit zina pellucida vaccines (Abstract), p4, 1993. Symp on contraception in Wildlife Management. Oct. 26-28. Denver Colorado.
[51]张宏利，韩崇选，杨学军，王明春，杨清娥，田海燕．鼠害防治方法研究进展．陕西林业科技，2004，(1)：41-47．
[52]Knipling EF, McGuire JU. Potential role of sterilisstion for suppressing rat populations-theoretical appraisal.Techn. Bull. Agric. Res. Service, U. S. Dept. Agric., 1972, p1455.
[53]杨春文．林业海鼠极其防治[M]．哈尔滨：黑龙江科技出版社，1991．
[54]张春美等．粗制棉籽粉、天花粉对小白鼠血清蛋白影响的研究．牡丹江师范学院学报，1994a，(2)．
[55]张春美等．复合不育剂对森林害鼠生殖阻断的研究．辽宁林业科技，1994b，3-4．
[56]付翠珍。棉毒素简介。中国棉花，1982,9(1)：45-48．
[57]石其贤，张国仪，裘金贤．服醋酸棉酚后男子精液脱落细胞的分析．中国药理学报，1981，(4)：262-266。
[58]男用节育药全国协作组．一种新小男性节育药—棉酚．中华医学杂志，1978，(8)：455-458．Tres L L.et al．Cell Biol Toxical，1992，8：61-67．
[59]张春美，陈荣，周维民．我国鼠类抗生育药剂的研究进展．Forest Pest and Disease，2001，(1)：34-35．
[60]庄凯勋，贾培峰，初德志等．应用植物不育剂控制林木鼠害新技术应用．中国森林病虫，2001，(增刊)：34-37．
[61]卢清显，沈晓明，程凯等．雷公藤总甙对大鼠生精作用及主要脏器的影响．中国医学科学院学报，1990,12(3)：203-206．
[62]张建伟，许烨，钱绍祯．雷公藤抗雄性生育成分的研究．实用男科杂志，1995，1(4)：75-78．
[63]张建伟，Stephen A M，Ana B等．雷公藤抗雄性生育成分的研究．实用男科杂 志，1995，(12)：75-77．
[64]张彬.雷公藤多苷(GTM)抗雄性生育活性的研究.中国现代医学杂志，2002，12 (4)：16-17．
[65]刘良，王战勇，黄光照，等．雷公藤甲素亚慢性中毒对昆明种小鼠肾脏及睾丸的影响．同济医科大学学报，2001，30(3)：214-217．
[66]Huynh PN, Hi Kim AP, Wang C, et al. Long-term effects of triptolide on sperm at ogendsis, epididymal sperm function, and fertility in male rats. J Androl, 2000, 21(5): 689-699.
[67]张建伟，董建孙，林宁等．雷公藤内酯酮对免疫功能的影响．中华男科学，2001，7(6)：377-379．
[68]张建伟，许烨，钱绍祯．草药雷公藤中的雄性抗生育有效成分．实用男科杂志，1996，2(2)：81-83．
[69]王士民，王薏，许烨，等．昆明山海棠对雄性大鼠抗生育作用的研究．江苏医药，1989(12)：659-660．
[70]马明福，蔡敏，李练兵，曾维三，李新生．昆明山海棠对人精子染色体的诱变作用研究。癌变．畸变．变变，2000，12(2)：90-92．
[71]方娜娜．昆明山海棠男性抗生育有效成分的研究．华西药学杂志，1987，2(3)：145.
[72]Riar SS，Devakurnar C，Ilavazhagan G et al．Volatile frac-tion of neem oil as a spermicide．Contraception，1990，42：479．
[73]Upadhyay SN，Kaushic C，Talwar GP．Antifertility effects of neem(Azadirachtaindica) oil by single intrauterine ad-ministration:a novel method for contraception．Proc Roy,Soc London,1990，242：175．
[74]Sinha KC，Riar SS，Tiwary RS，et al．Neem oil as a vagi-nal contraceptive．Indian J Med Rea，1984a，79：331．
[75]Labadie KP,Van der Nat JM，Simons JM，et al．Anethanopha：macognostic approach to the search for im-munomodulators of Plant origin．Planta Mediea，1989，55：339
[76]Lal K，Sankaranarayanan A，Methur VS，et al．Antifertility effect of neem oilinfemal alhino rats by the intravaginal oral routes．Indian J Med Res，1986，83：89．
[77]Deshpander VY, Mendulkar KV, Sadre NL. Make antifertility activity of Azadirachtuindica in mice: a preliminary report.J Postgra Med,1980, 26:167.
[78]Sinha KC, Kiar SS, Bardhan J, et al. Anti-implantation effect of neem oil.Indian J Med Res, 1984b, 80:708,
[79]中华人民共和国卫生部药典委员会编。中华人民共和国药典(一部)，1995版。广东科技出版社，pp．312-313。
[80]王慧．口服蓖麻油煎鸡蛋能缩短产程，中国民间疗法，2000，8(12)：46．
[81]向谋珍．蓖麻油煎蛋用于晚期妊娠引产效果观察，中国自然医学杂志，2005，7 (2)：86．
[82]Scarpa A., Guerci A. Various uses of the castor oil plant (Ricinus communis L.) a review. Journal of Ethnopharmacology, 1982, 5(2): 117-137.
[83]Okwuasaba FK, Das SC, Isichei CO, et al. The Anticonceptive and the Effect on Uterus of Ether Extract, 18312-J of Ricinus communis, Phytother Res, 1997a, 10:97-100.
[84]Okwuasaba FK, Das SC, Isichei CO, et al. Pharmacological Studies on the Antifertility Effects of RICOM-1013-J from Ricinus communis var minor and Preliminary Clinical Studies on Women Volunteers. Phytother Res, 1997b, 11:547-551.
[85]Das SC, Isichei CO, Okwuasaba FK, et al. Chemical, pathological and toxicological studies of the effects of RICOM-1013-J of Ricinus communis var minor on women volunteers and rodents.Phytother Res. 2000, 14:15-19.
[86]Isichei CO, Das SC, Ogunkeye OO, et al.Preliminary clinical investigation of the contraceptive efficacy and chemical pathological effects of RICOM-1013-J of Ricinus commnunis var minor on women volunteers. Phytother Res, 2000, 14: 40-42.
[87]Sandhyakumary K, Bobby RG and Indira M. Antifertility Effects of Ricinus communis (Linn) on Rats. Phytothearapy Research, 2003, 17, 508-511.
[88]秦晓娜，高平，甘明哲。蓖麻提取物对鼠抗生育作用研究。四川动物，2006，25(1)：176-179．
[89]陈萌．蓖麻籽油的成份分析．云南化工，1998，(2)：46-47．
[90]周继铭，余朝菁．抗生育中草药的研究．中成药，1990，12(1)：37-40．
[91]欧宁，王海琦，袁红宇等．马鞭草抗早孕作用的动物实验研究．中国药科大学学报，1999，30(3)：209-211．
[92]欧宁，袁红宇，蔡涛．马鞭草抗生育有效部位的实验研究．江苏中医，2001，22(1)：40-41．
[93]朱红梅，钟鸣，韦玉伍等．岗松根抗生育作用的实验观察．医学理论与实践，1995，8(4)：145-146．
[94]赵翠兰，江燕，李开源．朱槿花乙醇提取物对小白鼠的抗生育作用．云南中医中药杂志，1995，16(6)：57-58．
[95]何冰芳，陈琼华．黑木耳多糖对小鼠的抗生育作用．中国医科大学学报，1991，22(1)：48-49．
[96]王世祥，井文寅，车锡平等．怀牛藤总皂甙抗生育作用及其机理．西北药学杂志，1997，12(5)：209-211．
[97]贾瑞鹏，周性明，陈甸英．川楝子油对雄性大鼠的抗生育作用．南京铁道医学院学报，1996，15(1)：123．
[98]汪智军，王爱静．新疆灭鼠植物．中国野生植物资源，2002，21(6)：37-38．
[99]程立方，张淑真，崔秀君．中草药抗生育研究进展．时珍国药研究，1995，6(2)：45-46．
[100]陈鸿彬，张国柱，卢琦华等．棉酚对大小白鼠、家鼠抗生育作用的研究．中国媒介生物学及控制杂志，1990，1(1)：54．
[1]赵丹，谢达平．蓖麻毒蛋白研究进展．食与油脂，2005，(5)：3-5．
[2]汪多仁．蓖麻籽与蓖麻油应用进展．粮食与油脂，2000，(2)∶12-14．
[3]张建华，倪培德．蓖麻饼粕毒性成分分析及去毒的研究．中国油脂，1996，21(4)：22．
[4]Olsenes S, Alexander P. Different biological properties of the two constituent peptide chains of ricin, a toxic protein onhitibiting protein synthesis. Biochemistry, 1973, 12 (16).
[5]Philip J, et al. Structure and activity of an active site substitution of Ricin A chain. Biochemistry. 1996, 35: 11098-11103.
[6]Arthur E, et al. Ricin toxin contains at least three galactose-binding sites located in B chain subdomains 1a, 1B, and 2γ. Biochemistry. 1996, 35: 14794-14796.
[7] Rita M. et al. Identification of three oligosaccharide binding sites in Ricin. Biochemistry, 1999, 38: 11677-11685.
[8]罗嘉良．蓖麻毒素的研究与应用．氨基酸和生物资源．1999，21(2)：56．
[9]Lord J, et al. Ricin: structure, mode of action, and some current applications. FASEBJ., 1994, 8: 201-208.
[10]Ramesh Hegde, et al. Studies of the variants of the protein toxins Ricin and Abrin. Eur. J.Biochem.1992, 204, 155-164.
[11]鲁小青，陈百先，张今．蓖麻毒蛋白糖脂脂质体对肝癌细胞的杀伤作用及其理化特性．上海铁道大学学报(自然科学版)，1998，19(9)：24．
[12]Sandvig K, et al. Action of shiga toxin and Ricin. Physiological Reviews, 1996, 76: 949-966.
[13]Odal SK, et al. Extraction of cholesterol with methyl-a-cyclodextrin perturbs formation of clathrin-coated endocytic vesicles. Mol Biol Cell. 1999, 10: 961-974.
[14]Haft C R, et al. Taylor involvement of dileucine motifs in the internalization and degradation of the insulin receptor. J Biol Chem., 1994, 269: 26286-26294.
[15]Itin C F, et al. A novel endocytosis signal related to the KKXX ER-retrieval signal. EMBOJ., 1995, 14: 2250-2256.
[16]Sandvig K, et al. Pathways followed by ricin and shiga toxin into cells. Histochem Cell Biol., 2002,117: 131-141.
[17]Sadani G R, et al. Reactive oxygen species involvement in ricin-induced thyroid toxicity in rat. Hum Exp Toxicol., 1997, 16: 254-256.
[18]董巨莹等．蓖麻毒素对肝细胞有丝分裂原激活蛋白激酶的影响．中国生物化学与分子生物学报，2000,12：798-802．
[19]Yaeta Endo，et al．The mechanism of action of ricin and related toxic lectins on eukaryotic ribosomes．J Biol Chem.，1987，262：5908-5912．
[20]Xiang-Yang Chen，et al．Schramm Ricin A-chain：kinetics，mechanism，and RNA stem-loop inhibitors．Biochemistry，1998，37：11605-11613．
[21]Sandra W Key，et al．Researchers know beans about cancer research．Cancer Weekly Plus，1998．11：20．
[22]张晖，詹金彪．蓖麻毒素A链细胞内转机制研究．Journal of practical oncology，2002，17(3)：216．
[23]张今，秦德安．包有蓖麻毒蛋白的脂质体的制备、性质及毒性研究．生物化学与生物物理学报，1999，31(4)：472．
[24]张风春，胡奇芬，仲伯华．免疫毒素的非特异性毒性及其去除．中国药学杂志，1996，31(2)：70．
[25]Pattrick G, Richardson SW, Casolaro M ,et al. Poly (amdoamine)-mediated intracytoplasmic delivery of ricin A2chain and gelonin. Journal of cont rolled Release, 2001,77:225.
[26]Fred Wilson. Immunotoxin safely eliminates local inflammation in two days. Dermatology Times, 2000, 21: 18-19.
[27]Weiner L M, et al. Phase I evaluation of an antibreast carcinoma monoclonal antibody 260F9 ricin A chain. Cancer Res., 1989, 49: 4062-4067.
[28]张会等．包有蓖麻毒蛋白脂质体的制备、性质及毒性研究．生物化学与生物物理学报，1999,31：472-474．
[29]Chignola R, et al. Self-potentiation of ligand-toxin conjugates containing ricin A chain fused with vira 1 structures. The Journal of Biological Chemistry, 1995, 207: 23345-23351.
[30]沈演初．生物农药[M]．北京：化学工业出版社，2000，72-98．
[31]赵善欢．植物化学保护[M]．北京：中国农业出版社，2002，301-303．
[32]杜小凤等．植物源农药研究进展．农药，2000，(11)：8-10．
[33]尹秀玲等．蓖麻的开发利用．生物学杂志，1998，2：35．
[34]蔡东宏．用淘米水和蓖麻籽的熬出物防治椰子害虫．世界农业信息，1995，9．
[35]赵建兴等．蓖麻毒素粗提物杀虫作用的研究．内蒙古农业大学学报，2001,12：78-80.
[36]Maruniak J E, et al. Susceptibility of insect cells and ribosomes to ricin. Comparative Biochemistry and Physiology, 1990, 96: 543-548.
[37]Frigerio L, et al. The enemy within: Ricin and plant cells. Journal of Experimental Botany, 1998, 326: 1473-1480.
[38]陈萌．蓖麻籽油的成份分析．云南化工，1998，(2)：46-47．
[39]罗嘉惠、柳卫莉．蓖麻资源在能源、环境、医药和高科技领域中的应用．氨基酸和生物资源，1997，19(1)：44-46．
[40]Scarpa A, Guerci A. Various uses of the castor oil plant Ricinus communis. A review. J Ethnopharmacol, 1982; 5:117-37.
[41]Malhi BS, Trivedi VP. Vegetable antifertility drugs of India. Q J Crude Drug Res 1972;12:1922-1928.
[42]Woo WS, Lee EB, Shin KH, Kang SS, Chin HJ. A review of research on plants for fertility regulation in Korea. Kor J Pharmacogn 1981, 12:153-170.
[43]Brondegaard VJ. Contraceptive plant drugs. Planta Med 1973; 23:167-71.
[44]Salhab AS, Issa A, Alhougog I. On the contraceptive effect of castor beans. Int J Pharmacogn, 1997, 35:63-65.
[45]Salhab AS, Shomaf MS, Gharaibeh MN and Amer NA. Effects of Castor Bean Extract and Ricin A-Chain on Ovulation and Implantation in Rabbits.1999, 395-399.
[46]Okwuasaba FK, Das SC, Isichei CO, Ekwenchi MM, Onoruvwe O, Olayinka AO, Uguru VE, Dafur SJ, Ekwere EO, Parry O. The Anticonceptiveand the effect on uterus of ether extract 18312-J of Ricinus communis. Phytotherapy Research, 1997 (a), 10, 97-100.
[47]Isichei CO, Das SC, Ogunkeye OO, Okwuasaba FK, Uguru VE, Onoruvwe O, Olayinka AO, Dafur SJ, Ekwere EO and Parry O. Preliminary Clinical Investigation of the Contraceptive Efficacy and Chemical Pathological Effects of RICOM-1013-J of Ricinus communis var Minor on Women Volunteers. Phytother.Res. 2000, 14, 40-42.
[48]Das SC, Isichei CO, Okwuasaba FK, Uguru VE, Onoruvwe O, Olayinka AO, Ekwere EO, Dafur SJ and Parry O. Chemical, Pathological and Toxicological Studies of the Effects of RICOM-1013-J of Ricinus communis var Minor on Women Volunteers and Rodents. Phytother. Res. 2000, 14, 15-19.
[49]Sandhyakumary K, Bobby RG and Indira M. Antifertility Effects of Ricinus communis(Linn) on Rats. Phytother. Res. 2003, 17, 508-511.
[50] Okwuasaba FK, Das SC, Isichei CO, Ekwenchi MM, Onoravwe O, Olayinka AO, Uguru VE, Dafur SJ, Ekwereand EO, Parry O. Pharmacological Studies on the Antifertility Effects of RICOM-1013-J from Ricinus communis var minor and Preliminary Clinical Studies on Women Volunteers. Phytother. Res. 1997b, 11, 547-551.
[2]马玲．蓖麻餐在晚期妊娠引产中的应用．中华临床医药，2003，3(2)：21．
[3]杨宗梅．蓖麻油 米索前列醇用于足月引产临床比较．医药论坛杂志，2003，24(6)：62．
[4]Salhab AS, Shomaf MS, Gharaibeh MN, Amer NA. Effects of Castor Bean Extract and Ricin A-Chain on Ovulation and Implantation in Rabbits. Contraception,1999,59∶395-399.
[5]Abdulazim S. Salhab, Salah O. A1-Tamimi，Munir N. Gharaibehand Maha，et al. The Abortifacient Effects of Castor Bean Extract and Ricin-A Chain in Rabbits. Contraception，1998，58:193-197.
[6]ZHANG Chun-mei, WANG Rui-hong.Advance in the research of sterilants against rodents. Journal of Forestry Research, 2002，13(1): 77-81.
[7]Okwuasaba FK, Osunkwo UA, Ekwenchi MM, et al. Anticonceptive and estrogenic effects of a seed extract of Ricinus var. minor. Journal of Ethnopharmacology,1991, 34(2)∶141-145.
[8]Isichei CO, Das SC, Ogunkeye OO, Okwuasaba FK, Uguru VE, Onoruvwe O, Olayinka AO, Dafur SJ, Ekwere EO, Parry O. Preliminary Clinical Investigation of the Contraceptive Efficacy and Chemical Pathological Effects of RICOM-1013-J of Ricinus communis var Minor on Women Volunteers. Phytothearapy Research, 2000,14. 40-42.
[9]左风．蓖麻籽抗生育作用的毒理及临床研究．国外医学中医中药册，2901,23(5)∶286-287．
[10]Scarpa A, Guerci A. Various uses of the castor oil plant Ricinus communis. A review. JEthnopharmacol, 1982, 5∶117-137.
[11]Malhi BS，Trivedi VP. Vegetable antifertility drugs of India. Q J Crude Drug Res,1972, 12:1922-1928.
[12]Woo WS, Lee EB, Shin KH, Kang SS, Chin HJ.A review of research on plants for fertility regulation in Korea. Kor J Pharmacogn, 1981, 12∶153-70.
[13]Brondegaard VJ. Contraceptive plant drugs. Planta Med，1973，23∶167-71.
[14]Salhab AS, Issa A, Alhougog I.On the contraceptive effect of castor beans. Int J Pharmacogn 1997，35∶63-65.
[15]Das SC, Isichei CO，Okwuasaba FK，Uguru VE，Onoruvwe O，Olayinka AO，Ekwere E O, Dafur SJ, Parry O. Chemical, Pathological and Toxicological Studies of the Effects of RICOM-1013-J of Ricinus communis var Minor on Women Volunteers and Rodents. Phytothearapy Research，2000，14，15-19.
[16]Sandhyakumary K, Bobby RG and Indira M. Antifertility Effects of Ricinus communis (Linn)on Rats. Phytothearapy Research，2003，17，508-511.
[17]Okwuasaba FK, Das SC, Isichei CO, Ekwenchi MM, Onoruvwe O, Olayinka AO，Uguru VE，Dafur SJ，Ekwere EO, Parry O, The Anticonceptive and the effect on uterus of ether extract 18312-J of Ricinus communis. Phytothearapy Research，1997(a)，10，97-100.
[18]Okwuasaba FK, Das SC, Isichei CO, Ekwenchi MM, Onoruvwe O, Olayinka AO，Uguru VE, Dafur SJ，Ekwereand EO，Parry O. Pharmacological Studies on the Antifertility Effects of RICOM-1O13-J from Ricinus communis var minor and Preliminary Clinical Studies on Women Volunteers. Phytothearapy Research，1997，11，547-551.
[19]张知彬．鼠类不育控制的生态学基础．兽类学报，1995a，15(3)∶229-234．
[20]张知彬．鼠类种群数量的波动与调节．王祖望，张知彬主编．鼠害治理的理论与实践．北京：科学出版社．1996a，pp145-165．
[21]张知彬．我国草原鼠害的严重性及防治对策．中国科学院院刊，2003，(5)∶434-437．
[22]秦晓娜，高平，甘明哲．蓖麻提取物对鼠抗生育作用研究，四川动物，2006，25(1)∶176-179．
[23]吴小丽，蔡云清，赵岩，李世芬．蒲公英提取物对小鼠免疫功能的调节作用．南京医科大学学报(自然科学版)，2005，25(3)∶163-165．
[1]中华人民共和国药典编辑委员会，中华人民共和国药典(1995年版)，广东科学技术出版社，广州，pp.312-313．
[2]马玲．蓖麻餐在晚期妊娠引产中的应用．中华临床医药，2003，3(2)∶21．
[3]Malhi BS, Trivedi VP.Vegetable antifertility drugs of India. Q J Crude Drug Res,1972, 12: 1922-1928.
[4]Woo WS, Lee EB, Shin KH, Kang SS, Chin HJ. A review of research on plants for fertility regulation in Korea. Kor J Pharmacogn, 1981,12∶153-70.
[5]Okwuasaba FK, Das SC, Isichei CO，Ekwenchi M M, Onoruvwe O, Olayinka AO, Uguru VE,Dafur SJ, Ekwere EO and Parry O. The Anticonceptive and the Effect on Uterus of Ether Extract, 18312-J of Ricinus communis, Phytotherapy Research, 1997a,10, 97-100.
[6]Okwuasaba FK, Das SC, Isichei CO, Ekwenchi MM, Onoruvwe O, Olayinka AO, Uguru VE, Dafur SJ, Ekwereand EO, Parry O. Pharmacological Studies on the Antifertility Effects of RICOM-1013-J from Ricinus communis var minor and Preliminary Clinical Studies on Women Volunteers. Phytotheapy Reearch, 1997b, 11,547-551.
[7]Isichei CO, Das SC, Ogunkeye OO, Okwuasaba FK, Uguru V E, Onoruvwe O,Olayinka AO, Dafur SJ, Ekwere EO and Parry O. Preliminary Clinical Investigation of the Contraceptive Efficacy and Chemical Pathological Effects of RICOM-1013-J of Ricinus communis var Minor on Women Volunteers. Phytotheapy Reearch 2000, 14, 40-42.
[8]Das SC, Isichei CO, Okwuasaba FK, Uguru VE, Onoruvwe O, Olayinka AO, Ekwere EO, Dafur SJ and Parry O. Chemical, Pathological and Toxicological Studies of the Effects of RICOM-1013-J of Ricinus communis var Minor on Women Volunteers and Rodents. Phytotheapy Reearch, 2000, 14, 15-19.
[9]秦晓娜，高平，甘明哲。蓖麻提取物对鼠抗生育作用研究，四川动物，2006，25(1)∶176-179。
[10]Arici A, Matalliotakis I, Goumenou A, et al. Increased pregnancy-associated plasma protein-a(PAPP-A)concentrations in peritoneal fluid of women with endometriosis. Am J Reprod Immunol. 2003, 49(2)∶70-74.
[11]董源芬，宋扬。应用时间分辨荧光法测定妊娠相关血浆蛋白A的临床意义。中国优生与遗传杂志，2005，13(12)：55-56．
[12]刘蓓，章晓梅，邓莲。妊娠相关血浆蛋白A在辅助生殖医学中的研究进展国外医学计划生育(生殖健康分册)，2006，25(5)：260-263．
[13]张春美，陈荣，周维民．我国鼠类抗生育药剂的研究进展．Forest pest and Disease，2001，1∶34-35．
[14]方琳丽，王鲁华，奚宝珊．女性不孕症患者血清性激素水平的变化．放射免疫学杂志，2001,13(5)∶298．
[15]邓莲，章晓梅，李春华，李永刚 马艳萍，高梦莹，冯怀瑛。妊娠相关血浆蛋白-A与人绒毛膜促性腺激素在卵泡发育中的关系，生殖医学杂志，2005，14(5)∶280-283．
[16]杨文秀．苯乙烯对生殖内分泌和动情周期的影响．癌变.畸变．突变，1995，(6)∶358-360．
[17]李美芝主编．妇科内分泌学[M]．北京：人民军医出版社．2001，4．
[18]于学文，高成阁，金辉．雌激素的抗抑郁作用．中华妇产科杂志，2003，38(2)∶113－114．
[19]Hofbauer LC, Khosla S, Dunstan CR, et al. Estrogen stimulates gene expression and protein production of osteopmtegerin in human osteoblastic cells. Endocrinology, 1999,140∶4367-4370.
[20]米芳芳．雌激素生物作用的研究．中医药研究，2001，18(2)：48-49．
[21]陈志龙，1984，子宫内膜组织病理学．
[22]郑光，周志俊一，载旭峰，孙运光，郑捷，唐颖，孙毅．小鼠子宫增重试验检测六种常用有机磷农药拟雌激素样活性．Carcinogenesis，Teratogenesis and Mutagenesis．2004,16(4)：211-231．
[1]Okwuasaba FK, Das SC, Isichei CO, et al. The Anticonceptive and the Effect on Uterus of Ether Extract 18312-J of Ricinus communis. Phytother Res, 1997a, 10∶97-100.
[2]Okwuasaba FK, Das SC, Isichei CO, et al. Pharmacological Studies on the Antifertility Effects of RICOM-1013-J from Ricinus communis var minor and Preliminary Clinical Studies on Women Volunteers. Phytother Res, 1997b, 11:547-551.
[3]Das SC, Isichei CO, Okwuasaba FK, et al. Chemical, pathological and toxicological studies of the effects of RICOM-1013-J of Ricinus communis var minor on women volunteers and rodents. Phytother Res, 2000, 14∶15-19.
[4]Isichei CO, Das SC, Ogunkeye OO, et al. Preliminary clinical investigation of the contraceptive efficacy and chemical pathological effects of RICOM-1013-J of Ricinus comrnunis var minor on women volunteers. Phytother Res, 2000, 14:40-42.
[5]秦晓娜，高平，甘明哲．蓖麻提取物对鼠抗生育作用研究．四川动物，2006，25(1)∶176-179．
[6]陈浩宏，顾芝萍，游根娣，庄临之．人蜕膜细胞培养作为抗早孕药物筛选模型的研究．上海铁道大学学报，1998，19(11)∶1-3．
[7]张曙萱，王海琦，欧宁。马鞭草提取液对体外培养人早孕蜕膜细胞的影响。中国天然药物，2004，2(4)∶242-246．
[8]Okwuasaba, FK, Osunkwo, UA, and Ekwenchi, MM. et al. Anticonceptive and estrogenic effects of a seed extract of Ricinus communis var minor.J.Ethnopharmacol. 1991, 34, 141-145.
[9]程宝鸾等编。动物细胞培养技术，华南理工大学出版社，广州，2003，8．第一版，pp131-132．
[10]Carmichael J, William GD, Adi FG, et al. Evealuation of a tetrazolium-based semiautiomated colorimetric assay:assessment of chemosensitivity testing. Cancer Res, 1987, 47∶936.
[11]刘承权．抗着床抗早孕药物的药效学研究进展．中国药学杂志，1988，8(3)∶72－75．
[12]Wynn RM．子宫生物学．北京：人民卫生出版社，1980：pp214-215．
[13]冷颖，杨纫姝．钙调素拮抗剂对离体培养人蜕膜细胞形态和活力的影响．生殖与避孕，1997，17(2)∶76～81．
[1]中华人民共和国药典编辑委员会，中华人民共和国药典(1995年版)，广东科学技术出版社，广州，pp．312-313．
[2]王慧．口服蓖麻油煎鸡蛋能缩短产程．中国民间疗法，2000，8(12)∶46．
[3]潘丽，张瑞玲。妊娠晚期用蓖麻油引产餐引产的临床研究。中华现代临床医学杂志，2005,3(3)∶269-270．
[4]Okwuasaba FK，Das SC, Isichei CO, Ekwenchi MM, Onoruvwe O, Olayinka AO, Uguru VE, Dafur SJ, Ekwere EO, Parry O. The Anticonceptive and the effect on uterus of ether extract 18312-J of Ricinus communis. Phytotherapy Research 1997 (a), 10, 97-100.
[5]Okwuasaba FK, Das SC, Isichei CO, Ekwenchi MM, Onoruvwe O, Olayinka AO, Uguru VE, Dafur SJ, Ekwere EO, Parry O. Pharmacological studies on the antifertility effects of RICOM-1013-J from Ricinus communis var minor and preliminary clinical studies on women volunteers. Phytotherapy Research, 1997(b)，11，547-551.
[6]Isichei CO, Das SC, Ogunkeye OO, Okwuasaba FK, Uguru VE, Onoruvwe O, Olayinka AO, Dafur SJ, Ekwere EO, Parry O. Preliminary clinical investigation of the contraceptive efficacy and chemical pathological effects of RICOM-1013-J of Ricinus comrnunis var minor on women volunteers. Phytotherapy Research, 2000,14, 40-42.
[7]Das SC, Isichei CO, Okwuasaba FK, Uguru VE, Onoruvwe O, Olayinka AO, Ekwere EO, Dafur SJ, Parry O. Chemical, pathological and toxicological studies of the effects of RICOM-1013-J of Ricinus communis var minor on women volunteers and rodents. Phytotherapy Research, 2000, 14, 15-19.
[8]Sandhyakumary K, Bobby RG, Indira M. Antifertilit effects of Ricinus communis(Linn) on Rats. Phytotherapy Research, 2003,17, 508-511.
[9]秦晓娜，高平，甘明哲．蓖麻提取物对鼠抗生育作用研究．四川动物，2006，25(1)∶176-179．
[10]陈浩宏，顾芝萍，游根娣，庄临之．人蜕膜细胞培养作为抗旱孕药物筛选模型的研究．上海铁道大学学报，1998，19(11)∶1-3．
[11]Carmichael J, William GD, Adi FG，John DM, James BM, Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing. Cancer Research, 1987, 47∶936.
[12]陈萌．蓖麻籽油的成份分析．云南化工，1998，(2)：46-47．
[13] Mellanen, P, Petanen, T, Lehtimaki, J, Makela, S, Bylund，G，Holmbom, B, Mannila, E, Oikari, A, Santti, R. Woodderived estrogens: Studies in vitro with breast cancer cell lines and in vivo in trout. Toxicol. Appl. Pharmacol. 1996, 136, 381-388.
[14]Ethan DC, Alison CR. Behavioral changes in fish exposed to phytoestrogens Environmental Pollution. 2006,144, 833-839.
[15]Tarja N, Kirsti E. Effects of phytosterols on zebrafish reproduction in multigeneration test. Environmental Pollution, 2003,123, 267-273.
[16]Khan MR, Mlungwana SM. γ-Sitosterol, a cytotoxic sterol from Markhamia zanzibarica and Kigelia Africana. Fitoterapia, 1999, 70:96-97.
[17]高瑜莹，裘爱泳，谢光，陈宗杰．溶剂法富集豆甾醇的研究．中国油脂，2000，25(6)：159-162．
[18]许文林，王雅琼，鲁萍．脱臭馏出物中植物甾醇的回收和精制．过程工程学报，2002a，2(2)：167-170．
[19]许文林，王雅琼，黄一波，鲁萍．重结晶法精制植物甾醇的溶剂选择．扬州大学学报(自然科学版)，2002(b)：5(1)：58-61,70．
[1]王祖望，张自彬．害鼠治理的理论与实践[M]．北京：科学出版社．1996，pp344-366．
[2]李翰，徐守成．大通县森林病虫害发生趋势预测及防治策略．青海农林科技，1999，(3)：28-30．
[3]邓址．啮齿动物的生态与防治[M]．北京：北京师范大学出版社．1989，pp13-18．
[4]韩崇选，王明春，杨学军．安全型无公害灭鼠剂—克鼠星的研制．西北林学院学报，2002，17(3)：44-47．
[5]周梅花，马有国．平面直方图在森林病虫害防治中的应用．青海农林科技，1999，(1)：35-37．
[6]张知彬．我国草原鼠害的严重性及防治对策．中国科学院院刊，2003，(5)∶434-437．
[7]杨学军，韩崇选，王明春，张宏利，杨清娥，李继光，何燕．林区鼠害的无公害治理与生态环境保护对策．2003，95(3)∶54-57．
[8]赵树芹．谈天然林鼠害及其防治．黑龙江林业，2003,6∶27．
[9]张宏利，卜书海，韩崇选，杨学军，王明春，杨清娥，吕宁．鼠害及其防治方法研究进展．西北农林科技大学学报(自然科学版)，2003，31(增刊)：167-172．
[10]王廷正，李金钢，张越，等．黄土高原啮齿动物区系及鼢鼠成因分析[M]．黄土高原林区鼢鼠综合管理研究[M]．西安：西北大学出版社，1995．pp1-11．
[11]王明春，韩崇选，杨学军．克鼠星1号防治甘肃鼢鼠研究．西北林学院学报，1999，14(2)：51-56。
[12]韩崇选，杨学军，王明春．多效抗旱驱鼠剂的苗木处理方法与效果．西北林学院学报，2001，16(4)：41-45．
[13]许毅达．在西部地区推广“绿色灭鼠工程”．学会月刊，2002，11：28-29．
[14]夏瑞心，巩向日．我国森林鼠害防治对策．辽宁林业科技，1997，(6)：47-51．
[15]李忠杰．C肉毒杀鼠素干冻剂防治草原鼠害试验初报．宁夏农林科技，1998，(1)：30．
[16]王贵林，沈世英．C型肉毒梭菌毒素杀灭高原鼢鼠的初步研究．兽类学报，1988，8(1)：76-77．
[17]汪志刚，杨心茂，周俗．C型肉毒梭菌毒素灭鼠新技术示范推广初报．四川草原，1990，(3)：47-49,58．
[18]王振飞，次仁罗布．C肉毒梭菌毒素灭鼠试验．西藏畜牧兽医，1991，(4)：23-25．
[19]Knipling EF.Sterile male method of population control.Sci.1959，130-902.
[20]Davis DE. Principles for populationaontrolby gametocides. Tram.N.Am. Wildl.Conf, 1961,26:160
[21]Howard WE. Biocontrol and chemosterilants. In Pestcontrol: Biological, Physical and Selected Chemical Methods (Eds.)W W. Kilgore & R L doutt Academic Press, New York and London, 1967. pp343-386.
[22]高源.鼠类化学不育剂的发展.中国媒介生物学及控制杂志，1996, 7(6): 481-484.
[23]Caughley, G, Pech R. and Grice D. Effect of fertility control on a population’s productivity. Wildlife Research. 1992, 19: 623-627.
[24]张知彬．鼠类不育控制的生态学基础．兽类学报，1995a，15(3)：229-234．
[25]张知彬．免疫不育在动物数量控制上的应用前景．医学动物防制，1995b，11(2)： 194-197．
[26]张知彬．鼠类种群数量的波动与调节．王祖望，张知彬主编．鼠害治理的理论与实践．北京：科学出版社．1996a，pp145-165．
[27]Chamber, LK, Singleton GR and Hinds LA. Fertility control of wild mouse populations: the effects of hormonal competence and animposed level of sterility. Wildlife Research, 1999a, 26:579-591.
[28]Chambers, LK, Lawson MA and Hinds LA. Biological control of rodents the case for fertility control using immunocontr-ception. In∶Singleton, G. R., L. A. Hinds, H. Leris and Z. B. Zhang ed. Ecologically-based Rodent Management. A CIAR Monograph. 1999b, 59: 215-242.
[29]Marsh RE & Howard W E Prospects of Chemosterilant genetic control of rodents. Bull Wild Hlth Org. 1973,48: 309.
[30]Marsh RE. Chemo-sterilants for rodent control. In Rodent Pest Management (Ed.) I.Prakash, CRC Press, Florida.1988, 353-367.
[31]Ericsaon RJ. Alphechlorohydrin (Epiblocr): a toxicant sterilant as an alternative in rodent control.Proc.10ch Vet. Pest Conf. Monterty, Calif, 1982, 5-9.
[32]朱靖，张知彬．农牧业鼠害综合治理的研究现状及对策．农牧业情报研究，1988，7∶1-10．
[33]Meehan AP. Rats and Mice, Their Biology and Control.Rentokil Liruited, Susser, 1984.
[34]Griffith W. Epibloc rodenticide introduces a new concept in”long-term”rodent control. Pest Control Tachnol. 1983,11 (4):42,64,67.
[35]Ericaacon RJ. Male antifertility compounds: U-5897 as a rat chemosterilant, J Reprod. Fert., 1970, 22:213.
[36]Jones AR. The antifertility actions of a-chlorohydrin in the male.Life Sci, 1978, 25:1625.
[37]Andrews RV, Belknap RW. Efficacy of a-chlorohydrin in sewer rat control. J.Hyg, Canto, 1983, 91:359.
[38]Ericsson RJ. Alphachlorohydrin (Epibloc): a toxicant sterilant as an alternative in rodent.control. Proc. of Tenth Vertebrate Pest Conference (R. E. Marshed.). 1982, 6-9.
[39]Handel DJ. In: Pharmacology, Biology, and clinical application of an-drogens, Current status and future prospects,Proceedings for the Second International Androgen Workshop.Califomia:Wiey-Liss, 1996,395-407.
[40]Gao Y, Short RV. Use of an oestrogen, androgen or gestagen as a potential chemosterilant for control of rat and mouse population, J Rrprod.Fer,1993, 97:392.
[41]Jackson H. Antifertility substances.Pharmacol.Rev,1959.11:135.
[42]Meriggiola MC, Bremner WJ, Paulsen CA, et al. A combined regimen of cyproterone acetate and testerone enanthate as a potentially highly effective male contraceptive.J Clin Endocrinol Metab, 1996, 81:3018-3023.
[43]Gao Y, Short RV. Fertility control in wild mice after feeding with RU486 or methyl testosterone.J.Reprod.Fert, 1994,101:483.
[44]Benhamou B. A single amino acid that determines sensitivity of progesterone receptors to RU486, Science, 1992, 255:206
[45]Swerdloff RS, Bagatell CJ, Wang C, et al. Suppression of spermatogenesis in man induced by Nal-Glu gonadotropin releasing hormone antagonistand testosterone enanthate (TE) is maintained by TE alone.J Clin Endocrinol Metab, 1998, 83 (10):3527-3533
[46]张春美，陈荣，周维民．我国鼠类抗生育药剂的研究进展．中国森林病虫，2001(1)：34-35．
[47]Miller SE，Chamow SM，Baur AW，Liver C，Robery F，Dean J．Vaccination with a synthetic zona pellucida peptide produces long-term contraception in female mice．Science，1989，246：935-938．
[48]Miller LA．Comparative effiency of two immuno-contraceptive vaccines for controuing wild Norway rats(Abstract)．P6，1993 Symposium on Contraception in Wildlife Management Oct．Denver Colorado．26-28．
[49]Shaha C，Kaul S，Kini M，Chaudhury M，Anad R，Das C and Talwar GP．Immunization against LHRH without the use of Freud’s complete adjuvant．1986， p143-150. Immunological Approaches to Contraception and Promotation of Fertility (G.P. Talwar ed). Plenum Press, New York.
[50]Thompaon RD, Miller LA and Johns BE. White-tailed deer immuno-contraception using porcine zona pellucida and recombinant rabbit zina pellucida vaccines (Abstract), p4, 1993. Symp on contraception in Wildlife Management. Oct. 26-28. Denver Colorado.
[51]张宏利，韩崇选，杨学军，王明春，杨清娥，田海燕．鼠害防治方法研究进展．陕西林业科技，2004，(1)：41-47．
[52]Knipling EF, McGuire JU. Potential role of sterilisstion for suppressing rat populations-theoretical appraisal.Techn. Bull. Agric. Res. Service, U. S. Dept. Agric., 1972, p1455.
[53]杨春文．林业海鼠极其防治[M]．哈尔滨：黑龙江科技出版社，1991．
[54]张春美等．粗制棉籽粉、天花粉对小白鼠血清蛋白影响的研究．牡丹江师范学院学报，1994a，(2)．
[55]张春美等．复合不育剂对森林害鼠生殖阻断的研究．辽宁林业科技，1994b，3-4．
[56]付翠珍。棉毒素简介。中国棉花，1982,9(1)：45-48．
[57]石其贤，张国仪，裘金贤．服醋酸棉酚后男子精液脱落细胞的分析．中国药理学报，1981，(4)：262-266。
[58]男用节育药全国协作组．一种新小男性节育药—棉酚．中华医学杂志，1978，(8)：455-458．Tres L L.et al．Cell Biol Toxical，1992，8：61-67．
[59]张春美，陈荣，周维民．我国鼠类抗生育药剂的研究进展．Forest Pest and Disease，2001，(1)：34-35．
[60]庄凯勋，贾培峰，初德志等．应用植物不育剂控制林木鼠害新技术应用．中国森林病虫，2001，(增刊)：34-37．
[61]卢清显，沈晓明，程凯等．雷公藤总甙对大鼠生精作用及主要脏器的影响．中国医学科学院学报，1990,12(3)：203-206．
[62]张建伟，许烨，钱绍祯．雷公藤抗雄性生育成分的研究．实用男科杂志，1995，1(4)：75-78．
[63]张建伟，Stephen A M，Ana B等．雷公藤抗雄性生育成分的研究．实用男科杂 志，1995，(12)：75-77．
[64]张彬.雷公藤多苷(GTM)抗雄性生育活性的研究.中国现代医学杂志，2002，12 (4)：16-17．
[65]刘良，王战勇，黄光照，等．雷公藤甲素亚慢性中毒对昆明种小鼠肾脏及睾丸的影响．同济医科大学学报，2001，30(3)：214-217．
[66]Huynh PN, Hi Kim AP, Wang C, et al. Long-term effects of triptolide on sperm at ogendsis, epididymal sperm function, and fertility in male rats. J Androl, 2000, 21(5): 689-699.
[67]张建伟，董建孙，林宁等．雷公藤内酯酮对免疫功能的影响．中华男科学，2001，7(6)：377-379．
[68]张建伟，许烨，钱绍祯．草药雷公藤中的雄性抗生育有效成分．实用男科杂志，1996，2(2)：81-83．
[69]王士民，王薏，许烨，等．昆明山海棠对雄性大鼠抗生育作用的研究．江苏医药，1989(12)：659-660．
[70]马明福，蔡敏，李练兵，曾维三，李新生．昆明山海棠对人精子染色体的诱变作用研究。癌变．畸变．变变，2000，12(2)：90-92．
[71]方娜娜．昆明山海棠男性抗生育有效成分的研究．华西药学杂志，1987，2(3)：145.
[72]Riar SS，Devakurnar C，Ilavazhagan G et al．Volatile frac-tion of neem oil as a spermicide．Contraception，1990，42：479．
[73]Upadhyay SN，Kaushic C，Talwar GP．Antifertility effects of neem(Azadirachtaindica) oil by single intrauterine ad-ministration:a novel method for contraception．Proc Roy,Soc London,1990，242：175．
[74]Sinha KC，Riar SS，Tiwary RS，et al．Neem oil as a vagi-nal contraceptive．Indian J Med Rea，1984a，79：331．
[75]Labadie KP,Van der Nat JM，Simons JM，et al．Anethanopha：macognostic approach to the search for im-munomodulators of Plant origin．Planta Mediea，1989，55：339
[76]Lal K，Sankaranarayanan A，Methur VS，et al．Antifertility effect of neem oilinfemal alhino rats by the intravaginal oral routes．Indian J Med Res，1986，83：89．
[77]Deshpander VY, Mendulkar KV, Sadre NL. Make antifertility activity of Azadirachtuindica in mice: a preliminary report.J Postgra Med,1980, 26:167.
[78]Sinha KC, Kiar SS, Bardhan J, et al. Anti-implantation effect of neem oil.Indian J Med Res, 1984b, 80:708,
[79]中华人民共和国卫生部药典委员会编。中华人民共和国药典(一部)，1995版。广东科技出版社，pp．312-313。
[80]王慧．口服蓖麻油煎鸡蛋能缩短产程，中国民间疗法，2000，8(12)：46．
[81]向谋珍．蓖麻油煎蛋用于晚期妊娠引产效果观察，中国自然医学杂志，2005，7 (2)：86．
[82]Scarpa A., Guerci A. Various uses of the castor oil plant (Ricinus communis L.) a review. Journal of Ethnopharmacology, 1982, 5(2): 117-137.
[83]Okwuasaba FK, Das SC, Isichei CO, et al. The Anticonceptive and the Effect on Uterus of Ether Extract, 18312-J of Ricinus communis, Phytother Res, 1997a, 10:97-100.
[84]Okwuasaba FK, Das SC, Isichei CO, et al. Pharmacological Studies on the Antifertility Effects of RICOM-1013-J from Ricinus communis var minor and Preliminary Clinical Studies on Women Volunteers. Phytother Res, 1997b, 11:547-551.
[85]Das SC, Isichei CO, Okwuasaba FK, et al. Chemical, pathological and toxicological studies of the effects of RICOM-1013-J of Ricinus communis var minor on women volunteers and rodents.Phytother Res. 2000, 14:15-19.
[86]Isichei CO, Das SC, Ogunkeye OO, et al.Preliminary clinical investigation of the contraceptive efficacy and chemical pathological effects of RICOM-1013-J of Ricinus commnunis var minor on women volunteers. Phytother Res, 2000, 14: 40-42.
[87]Sandhyakumary K, Bobby RG and Indira M. Antifertility Effects of Ricinus communis (Linn) on Rats. Phytothearapy Research, 2003, 17, 508-511.
[88]秦晓娜，高平，甘明哲。蓖麻提取物对鼠抗生育作用研究。四川动物，2006，25(1)：176-179．
[89]陈萌．蓖麻籽油的成份分析．云南化工，1998，(2)：46-47．
[90]周继铭，余朝菁．抗生育中草药的研究．中成药，1990，12(1)：37-40．
[91]欧宁，王海琦，袁红宇等．马鞭草抗早孕作用的动物实验研究．中国药科大学学报，1999，30(3)：209-211．
[92]欧宁，袁红宇，蔡涛．马鞭草抗生育有效部位的实验研究．江苏中医，2001，22(1)：40-41．
[93]朱红梅，钟鸣，韦玉伍等．岗松根抗生育作用的实验观察．医学理论与实践，1995，8(4)：145-146．
[94]赵翠兰，江燕，李开源．朱槿花乙醇提取物对小白鼠的抗生育作用．云南中医中药杂志，1995，16(6)：57-58．
[95]何冰芳，陈琼华．黑木耳多糖对小鼠的抗生育作用．中国医科大学学报，1991，22(1)：48-49．
[96]王世祥，井文寅，车锡平等．怀牛藤总皂甙抗生育作用及其机理．西北药学杂志，1997，12(5)：209-211．
[97]贾瑞鹏，周性明，陈甸英．川楝子油对雄性大鼠的抗生育作用．南京铁道医学院学报，1996，15(1)：123．
[98]汪智军，王爱静．新疆灭鼠植物．中国野生植物资源，2002，21(6)：37-38．
[99]程立方，张淑真，崔秀君．中草药抗生育研究进展．时珍国药研究，1995，6(2)：45-46．
[100]陈鸿彬，张国柱，卢琦华等．棉酚对大小白鼠、家鼠抗生育作用的研究．中国媒介生物学及控制杂志，1990，1(1)：54．
[1]赵丹，谢达平．蓖麻毒蛋白研究进展．食与油脂，2005，(5)：3-5．
[2]汪多仁．蓖麻籽与蓖麻油应用进展．粮食与油脂，2000，(2)∶12-14．
[3]张建华，倪培德．蓖麻饼粕毒性成分分析及去毒的研究．中国油脂，1996，21(4)：22．
[4]Olsenes S, Alexander P. Different biological properties of the two constituent peptide chains of ricin, a toxic protein onhitibiting protein synthesis. Biochemistry, 1973, 12 (16).
[5]Philip J, et al. Structure and activity of an active site substitution of Ricin A chain. Biochemistry. 1996, 35: 11098-11103.
[6]Arthur E, et al. Ricin toxin contains at least three galactose-binding sites located in B chain subdomains 1a, 1B, and 2γ. Biochemistry. 1996, 35: 14794-14796.
[7] Rita M. et al. Identification of three oligosaccharide binding sites in Ricin. Biochemistry, 1999, 38: 11677-11685.
[8]罗嘉良．蓖麻毒素的研究与应用．氨基酸和生物资源．1999，21(2)：56．
[9]Lord J, et al. Ricin: structure, mode of action, and some current applications. FASEBJ., 1994, 8: 201-208.
[10]Ramesh Hegde, et al. Studies of the variants of the protein toxins Ricin and Abrin. Eur. J.Biochem.1992, 204, 155-164.
[11]鲁小青，陈百先，张今．蓖麻毒蛋白糖脂脂质体对肝癌细胞的杀伤作用及其理化特性．上海铁道大学学报(自然科学版)，1998，19(9)：24．
[12]Sandvig K, et al. Action of shiga toxin and Ricin. Physiological Reviews, 1996, 76: 949-966.
[13]Odal SK, et al. Extraction of cholesterol with methyl-a-cyclodextrin perturbs formation of clathrin-coated endocytic vesicles. Mol Biol Cell. 1999, 10: 961-974.
[14]Haft C R, et al. Taylor involvement of dileucine motifs in the internalization and degradation of the insulin receptor. J Biol Chem., 1994, 269: 26286-26294.
[15]Itin C F, et al. A novel endocytosis signal related to the KKXX ER-retrieval signal. EMBOJ., 1995, 14: 2250-2256.
[16]Sandvig K, et al. Pathways followed by ricin and shiga toxin into cells. Histochem Cell Biol., 2002,117: 131-141.
[17]Sadani G R, et al. Reactive oxygen species involvement in ricin-induced thyroid toxicity in rat. Hum Exp Toxicol., 1997, 16: 254-256.
[18]董巨莹等．蓖麻毒素对肝细胞有丝分裂原激活蛋白激酶的影响．中国生物化学与分子生物学报，2000,12：798-802．
[19]Yaeta Endo，et al．The mechanism of action of ricin and related toxic lectins on eukaryotic ribosomes．J Biol Chem.，1987，262：5908-5912．
[20]Xiang-Yang Chen，et al．Schramm Ricin A-chain：kinetics，mechanism，and RNA stem-loop inhibitors．Biochemistry，1998，37：11605-11613．
[21]Sandra W Key，et al．Researchers know beans about cancer research．Cancer Weekly Plus，1998．11：20．
[22]张晖，詹金彪．蓖麻毒素A链细胞内转机制研究．Journal of practical oncology，2002，17(3)：216．
[23]张今，秦德安．包有蓖麻毒蛋白的脂质体的制备、性质及毒性研究．生物化学与生物物理学报，1999，31(4)：472．
[24]张风春，胡奇芬，仲伯华．免疫毒素的非特异性毒性及其去除．中国药学杂志，1996，31(2)：70．
[25]Pattrick G, Richardson SW, Casolaro M ,et al. Poly (amdoamine)-mediated intracytoplasmic delivery of ricin A2chain and gelonin. Journal of cont rolled Release, 2001,77:225.
[26]Fred Wilson. Immunotoxin safely eliminates local inflammation in two days. Dermatology Times, 2000, 21: 18-19.
[27]Weiner L M, et al. Phase I evaluation of an antibreast carcinoma monoclonal antibody 260F9 ricin A chain. Cancer Res., 1989, 49: 4062-4067.
[28]张会等．包有蓖麻毒蛋白脂质体的制备、性质及毒性研究．生物化学与生物物理学报，1999,31：472-474．
[29]Chignola R, et al. Self-potentiation of ligand-toxin conjugates containing ricin A chain fused with vira 1 structures. The Journal of Biological Chemistry, 1995, 207: 23345-23351.
[30]沈演初．生物农药[M]．北京：化学工业出版社，2000，72-98．
[31]赵善欢．植物化学保护[M]．北京：中国农业出版社，2002，301-303．
[32]杜小凤等．植物源农药研究进展．农药，2000，(11)：8-10．
[33]尹秀玲等．蓖麻的开发利用．生物学杂志，1998，2：35．
[34]蔡东宏．用淘米水和蓖麻籽的熬出物防治椰子害虫．世界农业信息，1995，9．
[35]赵建兴等．蓖麻毒素粗提物杀虫作用的研究．内蒙古农业大学学报，2001,12：78-80.
[36]Maruniak J E, et al. Susceptibility of insect cells and ribosomes to ricin. Comparative Biochemistry and Physiology, 1990, 96: 543-548.
[37]Frigerio L, et al. The enemy within: Ricin and plant cells. Journal of Experimental Botany, 1998, 326: 1473-1480.
[38]陈萌．蓖麻籽油的成份分析．云南化工，1998，(2)：46-47．
[39]罗嘉惠、柳卫莉．蓖麻资源在能源、环境、医药和高科技领域中的应用．氨基酸和生物资源，1997，19(1)：44-46．
[40]Scarpa A, Guerci A. Various uses of the castor oil plant Ricinus communis. A review. J Ethnopharmacol, 1982; 5:117-37.
[41]Malhi BS, Trivedi VP. Vegetable antifertility drugs of India. Q J Crude Drug Res 1972;12:1922-1928.
[42]Woo WS, Lee EB, Shin KH, Kang SS, Chin HJ. A review of research on plants for fertility regulation in Korea. Kor J Pharmacogn 1981, 12:153-170.
[43]Brondegaard VJ. Contraceptive plant drugs. Planta Med 1973; 23:167-71.
[44]Salhab AS, Issa A, Alhougog I. On the contraceptive effect of castor beans. Int J Pharmacogn, 1997, 35:63-65.
[45]Salhab AS, Shomaf MS, Gharaibeh MN and Amer NA. Effects of Castor Bean Extract and Ricin A-Chain on Ovulation and Implantation in Rabbits.1999, 395-399.
[46]Okwuasaba FK, Das SC, Isichei CO, Ekwenchi MM, Onoruvwe O, Olayinka AO, Uguru VE, Dafur SJ, Ekwere EO, Parry O. The Anticonceptiveand the effect on uterus of ether extract 18312-J of Ricinus communis. Phytotherapy Research, 1997 (a), 10, 97-100.
[47]Isichei CO, Das SC, Ogunkeye OO, Okwuasaba FK, Uguru VE, Onoruvwe O, Olayinka AO, Dafur SJ, Ekwere EO and Parry O. Preliminary Clinical Investigation of the Contraceptive Efficacy and Chemical Pathological Effects of RICOM-1013-J of Ricinus communis var Minor on Women Volunteers. Phytother.Res. 2000, 14, 40-42.
[48]Das SC, Isichei CO, Okwuasaba FK, Uguru VE, Onoruvwe O, Olayinka AO, Ekwere EO, Dafur SJ and Parry O. Chemical, Pathological and Toxicological Studies of the Effects of RICOM-1013-J of Ricinus communis var Minor on Women Volunteers and Rodents. Phytother. Res. 2000, 14, 15-19.
[49]Sandhyakumary K, Bobby RG and Indira M. Antifertility Effects of Ricinus communis(Linn) on Rats. Phytother. Res. 2003, 17, 508-511.
[50] Okwuasaba FK, Das SC, Isichei CO, Ekwenchi MM, Onoravwe O, Olayinka AO, Uguru VE, Dafur SJ, Ekwereand EO, Parry O. Pharmacological Studies on the Antifertility Effects of RICOM-1013-J from Ricinus communis var minor and Preliminary Clinical Studies on Women Volunteers. Phytother. Res. 1997b, 11, 547-551.