Effects of Intraventricular Injection of Calmodulin Antagonist （Trifluoperazine） on Pregnancy in Rats

Injection of TFP (a specific antagonist of CaM) into the lateral ventricles of the rat brain on the fourth day of pregnancy causes marked antifertility effect in 83% of the rats (0% in the control group). Examination with the pontamone blue reaction for the implantation elucidated that the antifertitity effect was due to the blockage of implantation of the follicle. Injection of TFP into the lateral ventricles of the brain markedly reduced the concentration of CaM in hypothalamus, ovary and uterus. Serum progesterone was also reduced. However, injection glven on day 7 was ineffective to terminate the pregnancy. Injection given on certain time of pregnancy was able to reduce the cellular CaM content and to cause antifertitity. This finding demonstrated that CaM played an important rote during the course of pregnancy.     

双炔失碳酯类似物的抗生育活性研究

本文报道八个双炔失碳酯类似物的小鼠抗早孕、抗着床试验结果,同时考查了生物活性与油水分布系数之间的关系,发现抗早孕活性与油水分布系数之间为线性相关。双炔失碳半琥珀酸酯的抗早孕效果优于已用于临床的双炔失碳丙酸酯。     

土荆皮甲酸的抗生育作用和毒性

土荆皮甲酸(Pseudolaric acid A),是从金钱松(Pseudolarix kamepferi)的根皮中分离得到的一个新型的二萜类化合物,将其混悬于1%羧甲基纤维素中,经口服给药,对大鼠、仑鼠及狗均可产生明显的抗早孕作用,其抗早孕的有效剂量各为7.5mg/kg,60mg/kg,0.5mg/kg qd×3d,土荆皮甲酸经皮下及阴道给药也能产生明显的抗早孕作用,其对大鼠口服的ED_(50),LD_(50)及95%可信限是14.5(11.7～17.7)mg/kg和219.8(193～250)mg/kg,得治疗指数10.2。狗的亚急性毒性试验表明,土荆皮甲酸对狗的中毒作用主要为呕吐、腹泻、便血等消化道的症状,显微镜下可见胃肠道粘膜及粘膜下组织广泛的出血点,其它器官未见到明显的病理变化。     

胡萝卜籽挥发油的抗生育作用

胡萝卜籽挥发油对小鼠有抗着床,抗早、中和晚期妊娠作用。对大鼠也有抗着床作用。挥发油中的萜类碳氢化合物部位,对小鼠皮下注射抗早期妊娠的ED_(50)为2.9ml/kg,甲地孕酮和hCG能明显逆转其作用;对假孕小鼠蜕膜瘤有抑制作用,此作用不能被甲地孕酮拮抗,皮下注射于早孕大鼠24、48小时后血浆孕酮浓度明显下降。以上提示其抗早孕作用机制可能与抑制孕酮合成和蜕膜反应有关。此外,挥发油碳氢部分无雌激素和抗雌激素活性,低浓度时对早孕大鼠离体子宫的收缩活动没有影响,高浓度则表现抑制作用。     

复方壬苯醇醚-9栓对家兔抗生育作用和阴道刺激性实验研究

目的:观察复方壬苯醇醚-9栓对家兔的抗生育作用和阴道刺激性。方法:采用改良Eckstein方法,对性成熟雌性家兔进行阴道刺激性研究。结果:家兔抗生育实验结果表明,高、中、低剂量实验药物组的避孕率分别为 100％、80％和60％;阴道刺激炎症总分值分别为4．3、3．5、3．0。结论:在实验应用剂量下壬苯醇醚-9抗生育作用及对阴道刺激性在可接受范围内。     

雷公藤单体对大鼠睾丸间质细胞及支持细胞毒性与其抗生育作用不相关

本文用体外培养的睾丸间质细胞和支持细胞筛选了２２种从雷公藤根、皮中分离、纯化的单体，并选择其中对两种细胞杀伤作用强、弱不同的化合物ＴＷ－９，ＴＷ－５，ＴＷ－２８和ＴＷ－２７进行抗生育试验以及体外杀精试验。结果发现对两种细胞毒性作用最弱的ＴＷ－１９对大鼠有明显的抗生育作用；而毒性作用较强的ＴＷ－５，ＴＷ－２８和最强的ＴＷ－２７则无明显的抗生育作用。然而这四种化合物的体外杀精强度则依次为：ＴＷ－２７，ＴＷ－５，ＴＷ－１９，ＴＷ－２８。与它们的抗生育作用不相关。     

抗生育剂量雷公藤对小鼠脾NK细胞活性的调节作用

采用银染和MTT的方法,分别观察不同剂量雷公藤对雄性小鼠的附睾尾精子变化和脾NK细胞活性的影响。结果显示:雷公藤实验组附睾尾精子多为头部异常,大部分出现头尾分离和折断现象,精子活率及密度均明显低于对照组。雷公藤对小鼠脾NK细胞活性存在着明显的剂量效应关系,多甙组和雷公藤糖浆大剂量组对NK细胞活性抑制较明显,而中剂量组和小剂量组则对NK细胞活性影响不明显。结果提示:雷公藤糖浆在有效抗生育剂量下对小鼠脾NK细胞活性无明显影响,为重新评价雷公藤的药用价值及今后的临床应用提供了有意义的实验数据。     

杀微生物避孕凝胶剂的抗生育和抗菌作用研究

目的:观察杀微生物避孕凝胶剂的体外杀精、家兔抗生育和抗菌作用。方法:杀精试验采用改良的Sander-Crammer方法;家兔抗生育试验将家兔随机分为高、中、低3个剂量组,分别阴道给予凝胶剂48mg/kg,24mg/kg和12mg/kg,给药后10min与雄兔进行交配,21d后解剖并计算避孕率;抗菌实验用体外试管法观察凝胶剂的抗金黄色葡萄球菌、大肠埃希菌和白色念珠菌的作用。结果:在20s内最低体外杀精浓度为0.5mg/ml;3个剂量组家兔避孕率分别为100%、80%和20%;对金黄色葡萄球菌、大肠埃希菌和白色念珠菌的最低杀菌浓度分别为0.05625%、0.225%和0.45%。结论:研制的凝胶剂有明显的抗生育作用和抗上述3种致病菌作用。     

黄体生成素释放激素类似物抗生育作用机理的分析

本工作观察了在大鼠妊娠不同阶段LHRH类似物的抗生育作用以及利血平对LHRH类似物终止妊娠作用的影响。分别于大鼠妊娠2～4天、5～7天、7～9天或12～14天,每鼠每天皮下注射一次LHRH类似物(200μg),对照组注射等量生理盐水。为观察利血平对于LHRH类似物抗生育作用的影响,于大鼠妊娠2～4天或5～7天,注射LHRH类似物同时,皮下注射利血平(0.5mg/kg),对照组注射等量利血平。每组均于最后一次给药后72小时处死,处死前取血测定血清孕酮,处死后开腹,记录妊娠动物数及正常着床胎数,并分别称量卵巢、全子宫及胚胎重量。结果表明,于大鼠妊娠2～4天、5～7天或7～9天,LHRH类似物皆具有明显的抗生育作用,并使血清孕酮水平下降,但于妊娠12～14天给药,对妊娠则无明显影响。这一结果提示,LHRH类似物的抗生育作用有可能是通过垂体一卵巢轴系实现的。于大鼠妊娠5～7天,利血平可以反转LHRH类似物的终止妊娠作用,但在妊娠2～4天,利血平则不能拮抗LHRH类似物的抗生育作用。这一结果提示,着床前应用LHRH类似物的抗生育机理可能与着床期和着床后用药的抗生育机理不尽相同,至少在大鼠着床前期,LHRH类似物的抗生育机理中,通过垂体-卵巢轴系可能不起主要作用。     

Inhibition of T-type Ca(2+) currents in mouse spermatogenic cells by gossypol, an antifertility compound

Gossypol, a male antifertility compound isolated from cotton, has been proved to inhibit capacitation and the acrosome reaction in human and mammalian sperm. Here, by using whole-cell recording, we observed the effects of gossypol on Ca(2+) and Cl(-) currents in mouse spermatogenic cells obtained by mechanical dissociation. The results showed that gossypol concentration-dependently and irreversibly inhibited T-type Ca(2+) currents in the cells. When the concentration of gossypol was > or =5 microM, the currents were blocked completely. The time to current block was progressively shortened as the gossypol concentration was increased from 5 to 80 microM. Moreover, the drug increased the time constant of inactivation in a concentration-dependent manner, while it did not affect the activation of the current. The inhibitory effect on the T-type Ca(2+) current did not correlate with signaling mediated by G proteins and tyrosine phosphorylation. No obvious effect of gossypol on Cl(-) currents was observed. These data suggest that the gossypol-induced inhibition of T-type Ca(2+) currents could be responsible for the antifertility activity of the compound, indicating a possibility to use gossypol as a local contraceptive drug.