云南白药对大鼠生育力与早期胚胎发育毒性的影响  

Toxicity on Fertility and Early Embryo Development by Intragastrical Administration of Yunnan Baiyao in Rats

作　　者：周国亮[1] 张立将[1] 宋翼升[1] 闫俊岭 由振强[1] 张立群 王真 宣尧仙[1] 

机构地区：[1]浙江省医学科学院安全性评价研究中心,浙江杭州310052 [2]云南白药集团股份有限公司,云南昆明650118

出　　处：《中华中医药学刊》2014年第8期1886-1889,共4页Chinese Archives of Traditional Chinese Medicine

基　　金：国家科技部重大科技专项课题项目(2008ZX09202-005);浙江省卫生厅项目(2012RCB008);浙江省科学技术厅项目(2013F20005);浙江省中医药管理局项目(2014ZA016)

摘　　要：目的:评价云南白药对大鼠生育力及早期胚胎发育的毒性影响。方法:SD大鼠每天分别灌胃给予云南白药4.0、1.4、0.5 g·kg-1剂量和超纯水(以下简称"阴性对照")1.5 mL·kg-1。每天1次,连续给药4周和2周后将雄鼠和雌鼠按1∶1合笼,交配14 d,记录交配情况。雄鼠给药至交配结束,雌鼠给药至妊娠第6天。在整个试验过程中每天观察大鼠的一般反应,定期称量大鼠体重和摄食量。雌雄大鼠分别于妊娠第15天和交配结束后进行解剖检查,计算孕鼠黄体数、着床数、活胎数、死胎数吸收胎数等检查早期胚胎发育情况,睾丸、附睾、前列腺或卵巢、子宫称重并计算脏器系数。结果:云南白药3个剂量组分别与阴性对照组比较,各剂量组雄鼠体重增长缓慢,有剂量和时间关系,雌鼠体重增长无异常;仅高剂量组大鼠的摄食量略少于阴性对照组;高剂量组给药后出现流涎、活动减少、闭眼等症状,少数大鼠出现打喷嚏、挠嘴等反应;各组大鼠解剖脏器均未发现肉眼可见的异常;各剂量组交配率、妊娠率、合笼天数与阴性对照组均无显著性差异P>0.05;子宫连胎重、黄体数、着床数、着床前丢失数、活胎数、死胎数、吸收胎数等胚胎形成指标与及阴性对照组比较均无显著性差异;高剂量组睾丸系数、附睾系数、前列腺系数,中、低剂量组附睾系数高于阴性对照组(P<0.05或P<0.01)。结论:在本试验剂量条件下,SD大鼠从交配前到交配期直至胚胎着床期间灌胃给予云南白药,对雌雄大鼠有一定的亲代毒性作用,但并不影响大鼠的生育力及早期胚胎发育,大鼠的生育力及早期胚胎发育毒性的无毒性反应剂量(NOAEL)为4.0 g·kg-1。Objective ：To observe the toxicity effect of Yunan Baiyao on rat fertility and early embryo development. Method：Male and female SD rats were randomly divided into a negative control group and three experiment groups. Male rats were administered by intravenous injection at the doses of 0,0.5,1.4,4.0 g · kg^-1 for 28 days before mating and during the mating period,and female rats injected the same dose levels from 14 days before mating through 7 days after gestation. Male rats were sacrificed after mating,and prenatal rats were sacrificed on the 15th day of pregnancy. The pa- rameters of reproduction and embryonic development were measured. Result ： The body weights of male rats in three treat- ment groups were significantly lower than that in the control group. Food intake in male and female high group was lower than that of control group. After administration, the main manifestation of toxic effect was salivation, reduced activity, closed eyes in all rats in high group, and partly with sneezing or flexible mouth. The rats＇ fertility was not obviously abnor- mal. Testicles,epididymis ,prostate weight coefficient in high group and epididymis ,weight coefficient in middle and low groups were larger than those of control group （ P 〈 0.05 or P 〈 0.01 ）. Early embryonic development had no obvious ab- normalities. Conclusion：Yunan Baiyao showed no obvious toxic effect on rats＇ fertility and early embryonic development in the test dose range in spite of some mild maternal toxicity. No observed adverse effect level（NOAEL） of toxicity on fertility and early embryo development in Yunan Baiyao was 4.0 g · kg^-1.

关 键 词：云南白药 生育力 早期胚胎发育 发育毒性 

分 类 号：R965[医药卫生—药理学]