千里光、千柏鼻炎片和总生物碱大鼠胚胎毒性研究

Study on embryonic toxicity of Senecio scandens,Qianbai Biyanpian and total alkaloid from S. scandens in rats

目的:探讨千里光及其复方千柏鼻炎片的胚胎毒性及其特点,为妊娠期安全用药提供参考。方法:选取受孕SD雌性大鼠220只,随机分为对照组;环磷酰胺组(10mg·kg-1)、千里光水提物低、中、高剂量组(含生药7.5,15.0,30.0g.kg-1;千柏鼻炎片复方提取物低、中、高剂量组(含生药7.5,15.0,30.0g·kg-1;千里光总生物碱提取物低、中、高剂量组(含生药7.5,15.0,30.0g·kg-1等11组,于大鼠胚胎器官形成期(妊娠期第6～15天)给药,于妊娠期间定期称量母鼠体重和摄食量,称量子宫质量和胎仔体重,记录早期吸收胎、晚期吸收胎、F吸收胎、死胎、活胎、黄体以及着床腺数目和胎仔性别。对每只胎仔进行外观检查,测量胎仔的身长和尾长,并进行内脏检查和骨骼检查。结果:复方高剂量组的母鼠体重增长减缓,摄食量降低;各种受试物给药组均未见吸收胎明显增高,但水提物和总碱高剂量组的死胎百分数(分别为2.7%,3.36%)较对照组(0.0%)显著升高;总碱高剂量组的胎仔体重和身长明显降低。水提物、复方和总碱各剂量组均可见一定程度的骨骼发育异常,主要表现为囟门增大,顶骨、顶间骨、枕骨发育不全或枕骨缺失、颈椎弓发育不全,少数动物出现第14对肋骨等,剂量关系不明显。总碱组骨骼畸形发生的窝百分率高达80%,复方的死胎发生率和骨骼急性发生率相对较低。结论:千里光单味药及其复方均具有一定程度的胚胎毒性,主要表现为骨骼发育异常。尽管复方的胚胎毒性与单味药比较相对较低,但复方仍然能够造成部分动物胎儿骨骼畸形,因此建议千里光以及含千里光的复方在妊娠期禁用。

Objective： To investigate the characteristics of embryonic toxicity of Senecio scandens, its total alkaloid and Qianbat Biyanpian so that to provide guidance for the safety of medication during pregnancy. Method ： Two hundred and twenty pregnant SD rats were divided into 11 groups： control group, positive group （cyclophosphamide 10 mg·kg^-1）. Water extract of S. scandens （doses：7.5, 15.0, 30. 0 g herb of S. scandens per kilogram body weight respectively）. Qianbai Biyanpian and total alkaloid at the same doses levels with the water extract of S. scandens （ doses were expressed as herb of S. scandens per kilogram body weight）. The test articles were given to the pregnant rats by garage from day 6 to day 15 of pregnancy. Body weight and the food consumption of pregnancy rats, and fetal weight and length were measured. The number of absorbed and dead embryos was recorded. Fetuses were examined in viscus and bones. Result： Weight and the food consumption of pregnancy rats in high-dose of Qianbai Biyanpian and total alkaloids decreased. All treatment groups had no significant change in the number of absorbed embryos, but the stillbirths were significantly increased in high-dose groups of water extract and total alkaloids as compared with control group. Bone deformities such as fontanel expanding, hypoplasia of parietal bone, occipital bone and cervical arch were observed. Rib abnormality could also be seen in some rats. All water extract of S. scandens, Qianbai Biyanpian and total alkaloid could cause the bone abnormalities, but the percentage of bone deformities of total alkaloids was the highest （ up to 80% ）. Conclusion ： S. scandens and its total alkaloids, its formula Qianbai Biyanpian can cause rat skeletal deformities in fetuses when they were given during pregnancy. It is suggested that S. scandens and the product containing S. scandens should hot be used during pregnancy.