摘要
目的大鼠经口给予骆驼蓬子提取物,观察其毒性反应,判断其重复给药的毒性靶器官或靶组织,观察动物生育力与早期胚胎发育情况。为临床试验的起始剂量和重复用药安全剂量范围、监测指标提供参考。方法随机将大鼠分为对照组、骆驼蓬子提取物低(0.027g/kg)、中(0.054g/kg)、高(0.108g/kg)剂量组,分别经口给予相应浓度的骆驼蓬子提取物,1.0ml/100g·bw,1次/d。交配前雌性大鼠先给药3周,交配后继续给药。动物观察到阴栓后第15d安乐死,进行解剖观察,检查胎仔的存活和畸形情况,对黄体数、着床数、活胎数、死胎数进行计数,检测血液学指标,计算脏器重量及系数,获取生殖器官进行组织病理学检查。试验期间每日对动物进行一般观察,定期测定动物体重和摄食量。结果孕鼠妊娠期第4d、10d高剂量组体重显著降低(P<0.01、P<0.05),妊娠期7d高剂量组摄食量显著降低(P<0.05)。解剖观察,各给药组孕鼠的腹主静脉、肾静脉均产生病理学改变,且有一定数量的孕鼠有胃肠胀气情况。与溶媒对照组比较,骆驼蓬子提取物各给药组平均黄体数、平均着床数无显著变化,平均活胎数有所降低,高剂量组平均死胎数有所升高,但差异均无统计学显著性意义。血液学检测显示骆驼蓬子低剂量组孕鼠HCT、HGB升高(P<0.05);高剂量组EOS%降低(P<0.01)。血液生化指标显示骆驼蓬子低剂量组孕鼠ALB及低、中、高剂量组ALT均显著升高(分别为P<0.01、P<0.01、P<0.05、P<0.001),低、高剂量组ALP及高剂量组UREA均显著升高(分别为P<0.05、P<0.001、P<0.01),低、中、高剂量组CHO均升高(分别为P<0.05、P<0.01、P<0.05)。与溶媒对照组比较,骆驼蓬子中剂量组心脏重量显著降低(P<0.01);高剂量组肾上腺重量显著升高(P<0.01);中、高剂量组肝脏系数显著升高(均为P<0.01);高剂量组肾上腺系数显著升高(P<0.01)。组织病理学观察结果显示给药各组雌性大鼠肝肾均具一定例数的病理学改变。结论综合各项检测结果,骆驼蓬子提取物对孕大鼠可能具有一定的毒性作用。
Objective To observe the toxicity of Peganum harmala L extract by oral administration in rats,and to judge the toxic target organs or tissues of repeated administration,and thento observe the fertility and early embryonic development of animals.Methods Rats were randomly divided into control group,low dose(0.027 g/kg),medium dose(0.054 g/kg)and high dose(0.108 g/kg)group.The rats were given the corresponding concentration of Peganum harmala L extract orally for 1.0 ml/100 g.bw.once a day.Female rats were administered for 3 weeks before mating and continued to be administered after mating.The animals were euthanized on the 15th day after the vaginal plug was observed,andanatomical observation was carried out to check the survival and deformity of fetuses.The number of corpus luteum,implantation,number of live births and stillbirths were counted.Hematological indicators were detected,organ weight and coefficientwere calculated,and reproductive organs were obtained for histopathological examination.During the test,the animals were observedcarefullyevery day,and their body weight and food intake were measured regularly.Results The body weight of pregnant rats in high-dose group decreased significantly on the 4th and 10th day of pregnancy(P<0.01,P<0.05),and the food intake of high-dose group decreased significantly on the 7th day of pregnancy(P<0.05).Anatomical observation showed that the main abdominal vein and renal vein of pregnant rats in each administration group had pathological changes,and a certain number of pregnant rats had gastrointestinal flatulence.Compared with the vehicle control group,there were no significant changes in the average number of corpus luteum,implantation and live births.The average number of dead births increased in the high-dose group,but the difference was not statistically significant.Hematological test showed that HCT and HGB increased in low dose group(P<0.05);EOS%decreased in high dose group(P<0.01).Blood biochemical indexes showed that ALB and ALT in low,medium and high dose groups were significantly increased(P<0.01,P<0.01,P<0.05 and P<0.001),ALP and UREA in low and high dose groups were significantly increased(P<0.05,P<0.001,P<0.01).And CHO in low dose groups,medium and high dose groups were significantly increased(P<0.05,P<0.01 and P<0.05).Compared with the vehicle control group,the heart weight in the medium dose group was significantly lower(P<0.01).The weight of adrenal gland in high dose group increased significantly(P<0.01).The liver coefficient increased significantly in medium and high dose groups(P<0.01).The adrenal coefficient increased significantly in the high-dose group(P<0.01).Histopathological observation showed that the liver and kidney of female rats in each group had a certain number of pathological changes.Conclusion Based on the test results,the extract of Peganum harmala L may have a certain toxic effect on female pregnant rats.
作者
窦勤
马福昌
艾西木江·热甫卡提
尤力都孜·买买提
阿布都吉力力·阿布都艾尼
库尔班尼沙
罗福祥
DOU Qin;MA Fuchang;Aiximujiang Refukati;Youliduzi Maiaiti;Abudujilili Abuduaini;LUO Fuxiang;Kuerbannisha(Department of Toxicology Laboratory,Traditional Uyghur Medicine Institute of Xinjiang,Urumqi,830011,China)
出处
《新疆医学》
2022年第12期1410-1414,共5页
Xinjiang Medical Journal
基金
新疆维吾尔自治区公益性科研院所基本科研业务费专项资金项目(项目编号:KYGY2016183)
关键词
SD大鼠
骆驼蓬子
生殖毒性
SD rats
Peganum harmala L
Reproductive toxicity
作者简介
窦勤,女,硕士,研究员,研究方向:药理毒理;通信作者:罗福祥,男,硕士,助理研究员,研究方向:药理毒理,E-mail:1341329265@qq.com。
