[关键词]
[摘要]
目的 观察肠炎宁颗粒对幼龄大鼠可能引起的毒性反应和毒性靶器官,为临床应用提供参考。方法 雌性大鼠与雄鼠交配、受孕并生仔。从出生12 d的仔鼠中,筛选出128只(16窝,8只/窝)随机分入4组,每组每性别16只。仔鼠出生第13天,分别ig给予低、中、高剂量(2、4、8 g/kg)的肠炎宁颗粒,对照组给予去离子水,给药体积为10 mL/kg,连续给药31 d,分别于给药31 d和停药28 d次日剖杀。检测指标包括:一般症状、体质量、摄食量、睁眼、腹部出毛、空中翻正、自主活动、尿液、股骨长度、血液学、血清生化学、T淋巴细胞亚群、肉眼大体和镜下组织病理学检查。结果 与对照组比较,给药0~3 d,肠炎宁颗粒低、中、高剂量组雄鼠和低、高剂量组雌鼠的体质量增长、及高剂量组雌雄大鼠给药第3天体质量均明显降低(P<0.05、0.01);给药31 d,中、高剂量组雄鼠平均股骨长度偏短(P<0.01),高剂量组雌鼠红细胞(RBC)、血红蛋白(HGB)、红细胞容积(HCT)轻度降低(P<0.05),给药组脾脏髓外造血增多;停药28 d后均恢复。未见与药物有关的其他不良反应。结论 本实验条件下,肠炎宁颗粒大剂量长期给药可引起幼龄大鼠出现一些异常反应,但程度轻微,且可恢复。
[Key word]
[Abstract]
Objective To identify the major toxic effects and target organs of Changyanning granule in juvenile rats, and provide a reference for human clinical use. Methods The female rats were naturally bred by breeder male rats, and allowed to deliver their litters. At PND12, 128 pups from 16 litters (litters of eight pups each) were selected and randomly assigned to four groups (16 juvenile rats per sex per group). At PND13, the juvenile rats were gavaged with low, medium and high dose (2, 4 or 8 g/kg) of Changyanning granule or deionized water. The dose volume is 10 mL/kg. All animals were necropsied on the next day after a 31-day dose and a 28-day recovery respectively. Parameters evaluated included clinical observations, body weights, food consumption, eye opening, coat growth, air righting, locomotor activity, urinalysis, femur length, hematology, clinical chemistry, T lymphocyte subsets, gross pathology and microscopic pathology. Results compared with control group, the body weight gain of male rats in low, middle and high dose group and female rats in low, high dose group for 0-3 d, and the body weight of male and female rats in high dose group on the third day decreased significantly (P<0.05 and 0.01). After a 31-day of treatment, a decrease in mean femur length were noted in males of 4 and 8 g/kg groups (P<0.01). RBC, HGB and HCT showed decreases in femals of the 8 g/kg group (P<0.05). Morphologic examination of the spleens revealed extramedullary hematopoietic proliferation in all treated groups. After a 28-day recovery period, these changes were reversed. Conclusion Under the experimental condition, a mild adverse reactions were induced by Changyanning granule large dose long term administration in juvenile rats, but were reversible.
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[基金项目]
国家科技重大新药创制项目(2015ZX09501004);天津市科技计划项目(16PTGCCX00090)