米非司酮对大鼠的抗着床作用研究

研究了米非司酮对大鼠的抗着床作用。大鼠在妊娠d₁、d₂或d₃口服米非司酮10mg/kg,每天1次,连续3d,有显著的抗着床作用、大鼠妊娠d1单次给米非司酮40mg/ks无抗着床作用,妊娠d₂给40mg/ks,d₃给10mg/kg有显著的抗着床作用。给药组大鼠子宫内膜发育延迟,蜕膜不能形成,影响孕卵着床。     

氯霉素对着床前大鼠胚泡的遗传毒性

为评价氯霉素对着床前胚泡的遗传毒性作用，Wistar大鼠在妊娠d3ip氯霉素65mg／kg，165mg／kg，330mg／kg。孕鼠于妊娠d4处死取胚泡，观察微核率，具微核胚泡率及有关丝分裂指数等。结果表明氛霉素各剂量组的微孩率呈剂量依赖性增加，与对照组相比较均有极显著差异；具微核胚烟率与对照组相比无显著差异，但呈一定量效相关性；ip氯霉素330mg/kg时．平均细胞数显著减少，有丝分裂指数与对照相比较无显著差异。提示氯霉素对整体大鼠着床有胚胞具遗传毒性。     

18-甲基乙炔雌二醇-3-甲醚的药理

本文报告了18-甲基乙炔雌二醇-3-甲醚的激素活性和避孕作用。18-甲炔雌甲醚在幼年雌性小鼠能明显刺激子宫发育,说明有雌激素活性。经与炔雌醇-3-甲醚作效价比较,结果指出其雌激素活性约为炔雌醇-3-甲醚的1/50。当与雌二醇同时应用时,18-甲炔雌甲醚并不能对抗雌二醇引起的子宫发育,说明没有抗雌激素活性。用Claubcrg方法以及用大鼠蜕膜瘤方法进行的实验说明18-甲炔雌甲醚没有孕激素活性,但有明显的抗孕激素活性。在小鼠妊娠第1、2、3天经口给18-甲炔雌甲醚,每日1 mg/kg小鼠不能怀孕。在妊娠第6、7、8天给18-甲炔雌甲醚,小鼠只有10～20%怀孕。说明有明显的抗着床和抗早孕作用。在小鼠妊娠第1、2两天经口给18-甲炔雌甲醚,有4/10的动物在妊娠第四天输卵管中仍可见到受精卵,而对照组在妊娠第四天输卵管中都没有卵子,可见18-甲炔雌甲醚使受精卵在输卵管中的运行变慢,这一作用也可能是18-甲炔雌甲醚抗着床作用的一个原理。经口给小鼠18-甲炔雌甲醚2 mg/kg,连给2周,对动物体重增长和各主要脏器形态都没有明显影响。经口给狗1 mg/kg,连给两周,狗的血象、心脏和肝、肾功能没有出现异常。     

土茯苓抗生育活性与保肝作用的初步药理研究

土茯苓(Smilax glabra Roxb.)醇提取物的水部分分别以27、40、80g生药/kg/天的剂量给雌性小鼠于妊娠D_1—D_6ig6天,各组均有显著的抗着床活性;雌性大鼠用100g生药/kg/天ig 6天,也能明显提高抗着床率。但是,其醇提物中氯仿部分与正丁醇部分对小鼠均无明显作用,提示土茯苓中抗生育活性成分 具有一定的亲水性。此外,土茯苓煎剂分别以40、80g生药/kg ig一日2次,连续2天,均能明显降低CCl_4中毒小鼠血清谷丙转氨酶活性,表明其对小鼠的实验性肝损伤有保护作用。     

醋酸棉酚对雌性大鼠的抗早孕作用

大鼠于妊娠第6～9天,喂以醋酸棉酚80 mg/kg/d, 有明显的抗早孕作用。皮下注射孕酮5 mg/d或hCG 25 IU/d可拮抗醋酸棉酚的抗早孕作用。醋酸棉酚80 mg/kg/d对去卵巢后给以外源性雌酮和孕酮以维持妊娠的大鼠无抗早孕作用。正常妊娠大鼠,给醋酸棉酚后,血清孕酮水平下降,妊娠中止,若同时注射hCG,孕酮水平回升接近对照动物的水平,药物抗早孕作用消失,但仍低于单给hCG组大鼠血清孕酮水平,说明醋酸棉酚可阻断hCG促黄体分泌孕酮的作用,这可能是醋酸棉酚抗早孕作用的主要机理之一。     

吗啡不同剂量和给药时程对建立大鼠条件性位置偏爱模型的影响

目的：比较吗啡不同给药剂量及不同给药时程对建立大鼠条件性位置偏爱（cPP）模型的影响，用于建立满意的CPP模型。方法：分别采用15mg／kg吗啡连续颈背部皮下注射（SC）6d，10mg／kg吗啡连续颈背部皮下注射（SC）6d、8d、10d进行CPP训练，测定大鼠在伴药箱停留的时间。结果：与对照组比较，15mg／kg吗啡6d组、10mg／kg吗啡8d组和10mg／kg吗啡10d组大鼠在伴药箱停留的时间均明显延长（P〈0．05），诱导大鼠CPP建立，三组大鼠在伴药箱停留时间比较差异无统计学意义；10mg／kg吗啡训练大鼠6d后，与相应的生理盐水对照组比较，大鼠在伴药箱停留时间差异无统计学意义，未能诱导CPP形成。结论：大鼠在用10mg／kg吗啡训练8d、10d及15mg／kg吗啡训练6d后，均可诱导大鼠CPP形成，但10mg／kg吗啡训练8d建立的CPP模型较满意。     

左旋18-甲基炔诺酮肟与左旋18-甲基炔诺酮的抗生育作用比较

本文比较了LNGO和LNG对大鼠的抗生育作用,结果表明,LNGO在剂量为10mg/kg·d时可以完全抑制大鼠着床,剂量为40,60mg/kg·d时有明显抗早孕作用。光电镜观察提示,剂量为10mg/kg·d时,对大鼠子宫内膜间质细胞和上皮细胞均有影响。组织培养研究发现,对体外人胎盘滋养层细胞有直接损伤作用。LNG对大鼠未见抗着床及抗早孕作用,对大鼠子宫内膜和体外人胎盘滋养层细胞也均未见明显作用。     

氯霉素对着床前大鼠胚泡的遗传毒性

为评价氯霉素对着床前胚泡的遗传毒性作用,Wistar大鼠在妊娠d3ip氯霉素65mg/kg,165mg/kg,330mg/kg。孕鼠于妊娠d4处死取胚泡,观察微核率,具微核胚泡率及有关丝分裂指数等。结果表明氛霉素各剂量组的微孩率呈剂量依赖性增加,与对照组相比较均有极显著差异;具微核胚烟率与对照组相比无显著差异,但呈一定量效相关性;ip氯霉素330mg/kg时.平均细胞数显著减少,有丝分裂指数与对照相比较无显著差异。提示氯霉素对整体大鼠着床有胚胞具遗传毒性。     

蛇床子素抑制血栓形成及其作用机制研究

目的研究蛇床子素抑制血栓形成及其可能的作用机制。方法利用大鼠静脉血栓形成模型和动-静脉旁路血栓形成模型测定给予蛇床子素10mg／kg、20mg／kg、40mg／kg后血栓湿重和干重，同时在动-静脉旁路血栓形成模型中测定大鼠血清NO含量，血浆TXB2和6-keto—PGF1α的含量。结果蛇床了素20mg／kg、40mg／kg组可以明显抑制大鼠静脉血栓形成，减轻血栓湿重和于重；蛇床子素10mg／kg、20mg／kg、40mg／kg组可以明显抑制大鼠动-静脉旁路血栓形成，减轻血栓湿重和干重，同时增加血清中NO的含量，降低血浆中TXB2的含量和增加血浆中6-keto—PGF1α的含量。结论蛇床子素可明显抑制大鼠血栓形成．其作用机制可能与增加血清中NO的含量，降低血浆中TXB2的含量和TXB2/6-keto—PGF1α的比值有关。     

白介素-2的抗炎作用和免疫调节作用

研究重组人白介素-2(rhI卜2)的抗炎和免疫调节作用。选择小鼠鼠耳肿胀和大鼠足拓肿胀模型研究，hlL-2的抗炎作用；选择碳廓清率实验、迟发性变态反应实验研究rhIL2的免疫调节作用。RhlL-2注射液，剂量为20，10，5，2．5．1．25万u／kg时，对小鼠鼠耳肿胀模型有抑制作用，其中剂量为2．5～5万u／kg时，抑制率最大；剂量为2．5万u／kg时，对大鼠足拓肿胀模型有显著的抑制作用；rhIL-2注射液每日SC用药剂量为10万u／kg，连续给药9d后，可以明显增强小鼠单核吞噬细胞功能；rhIL-2注射液每日SC用药剂量为5万u／kg，连续给药6d后，可明显减轻由免疫抑制剂引起的小鼠迟发性变态反应降低的强度。rhIL-2在一定剂量范围内可以起到抗炎和免疫调节作用。     

Effects of subcutaneous administration of daidzein on blastocyst implantation in rats.

The study was conducted to investigate the effects of phytoestrogen daidzein on blastocyst implantation in rats. Following successful mating, female rats were given daidzein by subcutaneous administration at the dose of 0 (vehicle control, n=15), 50 mg/kg body weight (n=15) and 150 mg/kg body weight (n=15) daily on day 1-7 of pregnancy and were sacrificed on day 8 of gestation. The results revealed that high-dose treatment (150 mg/kg body weight) significantly diminished the rate of blastocyst implantation and serum levels of gonadotropin-releasing hormone (GnRH), progesterone, and gonadotropins (FSH and LH), meanwhile the serum level of beta endorphin increased significantly. These effects were not observed in the low-dose treatment group (50 mg/kg body weight). The results of this study suggested that the anti-implantation effects of daidzein are probably caused by the interference of the hypothalamus-pituitary-gonadal axis which is involved in the implantation process.     

Anti-implantation effect of droloxifene in rats and its relationship with anti-estrogenic activity

AIM: To investigate the anti-implantation effect of droloxifene and study the possible relationship between the anti-estrogenic activity of droloxifene and its anti-implantation effect. METHODS: Pregnant rats were treated orally with droloxifene at 10:00 AM on d 2 at doses of 1.25-20 mg/kg to observe anti-implantation effects, and then doses of 14 mg/kg or 2.5 mg/kg were given at different time on d 2 to d 5 to determine the optimal administration time for anti-implantation effects. Pregnant rats were treated with a combination of droloxifene (2.5 mg/kg, ig) and E2 (0.5-8.0 microg/kg, sc) on the optimal administration time to observe the antagonistic effect of external estrogen on the anti-implantation effect of droloxifene. Serum estrogen and progesterone levels were measured by carrying out radioimmunoassays on d 1 to d 6 in droloxifene-treated and control rats to determine the surge time for nidatory estrogen and the effect of droloxifene on ovary function. RESULTS: Droloxifene has anti-implantation effects in rats. The optimal oral administration time was at 22:00 PM on d 4, which was after the surge time for nidatory estrogen (on d 4 at 10:00 AM). This suggests that the anti-implantation effect of droloxifene is not attributable to antagonism of the surge in secretion of nidatory estrogen. External estrogen did not antagonize the anti-implantation effect of droloxifene. Droloxifene had no effect on the serum levels of estrogen and progesterone on d 5 or d 6 when administered on d 4 at 22:00 PM. CONCLUSION: Droloxifene has an anti-implantation effect in rats, and the effect appears to be not completely due to its anti-estrogenic activity.     

The characteristics of the embryotoxic action of kalipsol]

The effect of calipsol on the course of pregnancy and the embryonal development in albino rats was studied. It was found that single injections of the drug in a dose of 200 mg/kg on the 7th or 8th day of pregnancy induced no disorders in the pregnancy course and the embryonal development. At the administration in a dose of 40.0 mg/kg on the 11th, 13th, 15th days of pregnancy calipsol was shown to exert a marked embryolethal action and at the administration on the 7th, 9th, 11th days of pregnancy in doses of 20 and 40 mg/kg increased the number of fetuses with hemorrhages into the internal organs.     

米非司西酮用于足月孕鼠引产后母仔安全性的观察

目的 探讨米非司酮用于足月孕鼠引产对仔鼠及母鼠的安全性影响。方法 妊娠大鼠36只,随枘发成三组,妊娠第18天给予不同剂量米非司酮（0、1.6mg/kg、10mg/kg）,每组9只48小时后处死;另3只自然分娩,观察出生一周内的仔鼠生长发育状况。结果 仔鼠出生一周时心、肺、肝、肾、脑的形态指标无异常,生长发育良好。母鼠用药2周后的心、肺、肝、肾、脾的形态学观察与血常规、肝肾功能检测未发现剂量相关性改变。结论 米非司酮在选用的剂量范围和实验条件下,用于足月妊娠引产是安全的。     

Reproductive effects of ethnomedicinal formulation of tape-vine leaves in female rats

Documented ethno-contraceptive use of Tape-vine or Stephania japonica (THUNB.) MIERS., Syn. Stephania hernandifolia (WILLD.) WALP. leaves is evaluated with regards to post-coital pregnancy interceptive activity of its aqueous extract (AE) and an ethnomedicinal formulation (EF) in Wistar rats. EF at 500 and 250 mg/kg doses induced 66.7% and 33.3% post-coital pregnancy interception respectively and the higher dose exhibited significant reduction in number of litters born and also anti-implantation property. In contrast, none of the dose levels of AE interfered in pregnancy but significant anti-implantation property was observed at doses of 2 and 1 g/kg, even as the higher dose produced significant reduction in number of litters born as well. EF at 500 mg/kg also exhibited significant uterotrophic activity and histological changes in uterus. Pair-wise comparison of sex hormone-levels exhibited significant increment in serum estradiol, LH and FSH but decrease in progesterone levels. Assessed blood lipid-carbohydrate profile exhibited substantial decrease in glucose, cholesterol, VLDL and triglyceride contents and significant increase in HDL. It is concluded that EF probably acts as better post-coital pregnancy interceptive agent through restriction of implantation by alteration of gonadal hormone levels and decline in blood-glucose levels that possibly disrupts oxidative energy metabolism in uterus during implantation. High surge in LH and FSH suggests negligible interference in ovulatory mechanism. This preparation also seems to be free of cardiovascular risk factors. HPTLC and HPLC analysis of both EF and AE exhibited marked chemical differences.     

Pre-implantation embryonic loss induced by tributyltin chloride in rats

The effect of tributyltin chloride (TBTC1) administered during early pregnancy on pregnancy maintenance was evaluated in rats. Inseminated females were orally administered TBTC1 at a dose of 0, 8.1, 12.2 or 16.3 mg/kg on day 0 through day 7 of pregnancy. Females were sacrificed on day 20 of pregnancy and pregnancy outcome was determined. Pregnancy failure, which was evidenced by absence of implantation sites, was found in 0 of the 10, in 2 of the 11, in 10 of the 14 and in 10 of the 13 females at 0, 8.1, 12.2 and 16.3 mg/kg, respectively. The rate of pregnancy failure was significantly higher in the 12.2 and 16.3 mg/kg groups than that in the control group. In females with successful pregnancy, the numbers of corpora lutea, implantations and post-implantation loss per litter were comparable across all groups. No increase in the incidence of malformed fetuses was found in any TBTC1-treated groups. Thus it appears that TBTCl causes pregnancy failure after administration during very early pregnancy.     

Contraceptive and Estrogenic Effect of a Methanol Extract of Cassia nigricans Leaves in Experimental Animals

The methanol extract of Cassia nigricans Vadl leaves was investigated for its contraceptive activity in mice and rats. The extract dose-dependently (0.5–1.0 g/kg) protected the animals from conception for 1–4 gestational periods in mice and rats. It inhibited fetal implantation, as was confirmed by laparotomy on day 10 of pregnancy. The pups showed significant change in weight and length (p < 0.01) with 0.75 g/kg, compared to control fetal defects. In ovariectomized immature young rats and mice, there was a dose-dependent increase in uterine wet weight (p < 0.001). The extract induced uterotrophic effects or immature vaginal opening and cornification when compared with estrogen-treated groups. Its anticonceptive effect may be due in part to its anti-implantation, estrogenic and/or direct effect on the uterus.     

Teratogenic assessment of carbadox in rats

Carbadox was administered by gavage once daily to pregnant rats at doses of 0 (control), 10, 25, 50 or 100 mg/kg on days 8 through 15 of pregnancy. The dams were killed on day 21 and the number of implantation sites, resorptions and live fetuses were counted. A significant dose-related decrease in maternal body weight gains during treatment (days 8 through 15 of pregnancy) occurred at doses of 10 mg/kg and above. There was a dose-related decrease in fetal body weights which was statistically significant at 25 mg/kg and above. This compound showed not only embryolethal but teratogenic effect. Resorption rates were 81.8% at 100 mg/kg, occurring complete resorptions in five dams, compared with 3.4% resorption rate in the control. In fetal examinations, a significant increase in the incidence of external, skeletal and internal malformations occurred at 100 mg/kg, where the surviving fetuses born to dams with 40-93% resorptions had any malformations, short tail; kinky tail; brachygnathia or ectrodactyly.     

Embryolethal and teratogenic effects of bromofenofos in rats

Bromofenofos, an organophosphorus anthelmintic, was administered by gavage to rats as a single dose (50 mg/kg) on one of days 6 through 14 of pregnancy. The dams were killed on day 21, and the fetuses were removed, weighed and examined by routine teratological methods. A significant increase in fetal resorptions occurred after administration on days 9 through 13, with a maximum on day 10. Approximately 72% of the implants were resorbed after administration on day 10. Fetal body weights were significantly decreased when dams were treated on day 8 or later. The greatest decrease in fetal body weights was observed on day 10, when the fetuses weighed less than the controls by about 44% on the average. The incidence of fetuses with gross, skeletal and internal malformations was significantly increased on days 8 through 10, on days 8 through 11 and on days 8 and 9, respectively. Although various types of malformations were observed, most of them occurred on day 8, when no significant increase in fetal resorptions did occur. Cleft lip, short tail, brachygnathia, anal atresia, absence of genital tubercle, fused pelvic legs and perineal testicles were seen on day 8 as gross malformations. Skeletal malformations mainly affected the vertebrae and ribs. Major internal malformations on day 8 were hydronephrosis, hydroureter, anophthalmia, cleft palate, agenesis of the bladder and renal agenesis. Anophthalmia and/or microphthalmia were observed on days 8 through 10, with the highest incidence on day 9. To further determine the no-effect levels for embryolethal and teratogenic effects, a single dose of 10, 20, 30 or 40 mg/kg was administered by gavage to rats on days 8 or 10 of pregnancy. The no-effect levels of single oral dose for embryolethal and teratogenic effects were considered to be 40 and 30 mg/kg, respectively.