银杏内酯B注射液对大鼠生育力及早期胚胎发育毒性研究
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摘要
目的观察银杏内酯B(GGB)注射液对SD大鼠生育力及早期胚胎发育毒性。方法 SD大鼠随机分为GGB注射液低、中、高剂量(30、60、120 mg/kg,分别相当于临床等效剂量的52、105、210倍)组及溶媒对照组(生理盐水),每组雌雄各25只。每天尾静脉推注给药1次,雄鼠连续给药4周,雌鼠连续给药2周,以1∶1合笼交配,雄鼠继续给药至交配成功,雌鼠继续给药至妊娠第7天。在确定雌鼠受精后处死同笼的雄鼠,解剖检查睾丸和附睾等生殖器官及精子的数量、活力和形态。雌鼠妊娠第14天处死,解剖检查卵巢、子宫和胚胎的情况。结果雄性大鼠GGB注射液高剂量组给药2.5、3.0、3.5、4.0周体质量与溶媒对照组比较显著增高(P<0.05),雄性大鼠给药第2周中、高剂量组摄食量与溶媒对照组比较显著增高(P<0.05、0.01),给药第3周高剂量组摄食量与溶媒对照组比较亦显著增高(P<0.01),摄食量的增高与体质量的显著性增长呈现出较好的一致性,说明供试品对体质量的影响跟饲料的摄入有关。GGB注射液对雄性大鼠的睾丸、附睾的质量及脏器系数、精子数量、精子活力、精子形态没有显著影响;对雌鼠的体质量、摄食、孕鼠的黄体、活胎、死胎、吸收胎、着床数、交配率、受孕率、着床前丢失率和着床后丢失率没有显著影响。结论在本试验条件下,未见GGB注射液对大鼠的生育力及早期胚胎的发育有毒性作用。
Objective To study the toxicity effect of Ginkgolide B(GGB) Injection on fertility and early embryonic development in rats. Methods A total of 100 male and 100 female SD rats were randomly divided into four groups: low, medium and high dosage groups of GGB Injection(30, 60 and 120 mg/kg, 52, 105 and 210 times of clinical equivalent dose, respectively) and solvent control group(normal sodium). There were 25 male and 25 female rats in each group. The rats were given by caudal vein injection(l mL/100 g) once daily; The male rats were received successive administration for 28 days before mating and the successive administration of 14 days before mating to 7 days after pregnancy for female rats. When the female rats were confirmed to be pregnant,the male rats were executed and their testicle,epididymis and sperm were examined.The female rats were executed on the fourteenth day of pregnancy, and The ovary, uterus and embryo of the female rats were studied. Results To male rats, there was a significant increasing difference for the treatment group(120 mg/kg) compared with the control group in body weight gain of male rats in 2.5, 3, 3.5, and 4 week(P < 0.05), and the food intake of male rats in medium and high dose group was significantly higher than that in solvent control group at the second week(P < 0.05, 0.01), and the food intake of high dose group was also significantly higher than that in solvent control group at the third week(P < 0.01). The body weight gain may caused by food intake. There were no significant differences in mass and organ coefficients of testis and epididymis, sperm count, sperm viability, and sperm form. To female rats, there were no significant differences in the body weight, food intake, pregnancy rate,the number of corpus luteum, live embryo, dead embryo and absorbed embryo, implantation, mating rate, and the rate of lost oosperm before and after implantation. Conclusion Within the range of experiment doses,there is no significant toxic effect of GGB Injection on the fecundity and the early developme of embryo.
Objective To study the toxicity effect of Ginkgolide B(GGB) Injection on fertility and early embryonic development in rats. Methods A total of 100 male and 100 female SD rats were randomly divided into four groups: low, medium and high dosage groups of GGB Injection(30, 60 and 120 mg/kg, 52, 105 and 210 times of clinical equivalent dose, respectively) and solvent control group(normal sodium). There were 25 male and 25 female rats in each group. The rats were given by caudal vein injection(l mL/100 g) once daily; The male rats were received successive administration for 28 days before mating and the successive administration of 14 days before mating to 7 days after pregnancy for female rats. When the female rats were confirmed to be pregnant,the male rats were executed and their testicle,epididymis and sperm were examined.The female rats were executed on the fourteenth day of pregnancy, and The ovary, uterus and embryo of the female rats were studied. Results To male rats, there was a significant increasing difference for the treatment group(120 mg/kg) compared with the control group in body weight gain of male rats in 2.5, 3, 3.5, and 4 week(P < 0.05), and the food intake of male rats in medium and high dose group was significantly higher than that in solvent control group at the second week(P < 0.05, 0.01), and the food intake of high dose group was also significantly higher than that in solvent control group at the third week(P < 0.01). The body weight gain may caused by food intake. There were no significant differences in mass and organ coefficients of testis and epididymis, sperm count, sperm viability, and sperm form. To female rats, there were no significant differences in the body weight, food intake, pregnancy rate,the number of corpus luteum, live embryo, dead embryo and absorbed embryo, implantation, mating rate, and the rate of lost oosperm before and after implantation. Conclusion Within the range of experiment doses,there is no significant toxic effect of GGB Injection on the fecundity and the early developme of embryo.
引文
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[9]龚华云,李宗河,范小艳,等.新型PPAR-δ激动剂对SD大鼠生育力与早期胚胎发育毒性研究[J].国外医药(抗生素分册), 2015, 36(5):216-222.
[10]谷颖敏,李咏梅,姜昕,等.朱砂灌胃给药对大鼠生育力与早期胚胎发育毒性的研究[J].中国实验方剂学杂志, 2011, 17(9):226-231.
[11]岳鹏,沈姣,蔡鸣,等.赤苷脉通注射液对大鼠生育力和早期胚胎发育的毒性研究[J].华西药学杂志,2016, 31(2):162-164.
[12]孙祖越,周莉,闫晗,等.如何成功开展药物非临床生殖毒性试验[J].中国新药杂志, 2011, 20(22):2195-2204.
[2]黄晓舞,梅世昌,李外.银杏内酯B注射液对Beagle犬的长期毒性研究[J].中国药房, 2008, 19(30):2338-2341.
[3]国家食品药品监督管理局.药物生殖毒性研究技术指导原则[S]. 2006.
[4]中华人民共和国卫生部药政局.新药(西药)临床前研究指导原则汇编(药学、药理学、毒理学)[S]. 1993.
[5]袁伯俊,王治乔.新药临床前安全性评价与实践[M].北京:军事医学科学出版社, 1997.
[6]叶向锋,王灵芝,王爱平. SJX对SD大鼠生育力与早期胚胎发育的影响[J].中国药理学与毒理学杂志, 2013,27(3):610.
[7]张彤,汪晶,龚夏实,等.中药DMY对大鼠Ⅰ段生殖毒性作用[J].中国药理学与毒理学杂志, 2013, 27(3):592-593.
[8]邓沁,吴忠,彭维,等.一类新药尖吻蝮蛇凝血酶对SD大鼠生育力和早期胚胎发育的影响[J].中南药学, 2017, 15(8):1032-1036.
[9]龚华云,李宗河,范小艳,等.新型PPAR-δ激动剂对SD大鼠生育力与早期胚胎发育毒性研究[J].国外医药(抗生素分册), 2015, 36(5):216-222.
[10]谷颖敏,李咏梅,姜昕,等.朱砂灌胃给药对大鼠生育力与早期胚胎发育毒性的研究[J].中国实验方剂学杂志, 2011, 17(9):226-231.
[11]岳鹏,沈姣,蔡鸣,等.赤苷脉通注射液对大鼠生育力和早期胚胎发育的毒性研究[J].华西药学杂志,2016, 31(2):162-164.
[12]孙祖越,周莉,闫晗,等.如何成功开展药物非临床生殖毒性试验[J].中国新药杂志, 2011, 20(22):2195-2204.