目的 觀察腸炎寧顆粒對幼齡大鼠可能引起的毒性反應(yīng)和毒性靶器官，為臨床應(yīng)用提供參考。方法 雌性大鼠與雄鼠交配、受孕并生仔。從出生12 d的仔鼠中，篩選出128只（16窩，8只/窩）隨機(jī)分入4組，每組每性別16只。仔鼠出生第13天，分別ig給予低、中、高劑量（2、4、8 g/kg）的腸炎寧顆粒，對照組給予去離子水，給藥體積為10 mL/kg，連續(xù)給藥31 d，分別于給藥31 d和停藥28 d次日剖殺。檢測指標(biāo)包括：一般癥狀、體質(zhì)量、攝食量、睜眼、腹部出毛、空中翻正、自主活動、尿液、股骨長度、血液學(xué)、血清生化學(xué)、T淋巴細(xì)胞亞群、肉眼大體和鏡下組織病理學(xué)檢查。結(jié)果 與對照組比較，給藥0~3 d，腸炎寧顆粒低、中、高劑量組雄鼠和低、高劑量組雌鼠的體質(zhì)量增長、及高劑量組雌雄大鼠給藥第3天體質(zhì)量均明顯降低（P<0.05、0.01）；給藥31 d，中、高劑量組雄鼠平均股骨長度偏短（P<0.01），高劑量組雌鼠紅細(xì)胞（RBC）、血紅蛋白（HGB）、紅細(xì)胞容積（HCT）輕度降低（P<0.05），給藥組脾臟髓外造血增多；停藥28 d后均恢復(fù)。未見與藥物有關(guān)的其他不良反應(yīng)。結(jié)論 本實(shí)驗(yàn)條件下，腸炎寧顆粒大劑量長期給藥可引起幼齡大鼠出現(xiàn)一些異常反應(yīng)，但程度輕微，且可恢復(fù)。

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.

國家科技重大新藥創(chuàng)制項(xiàng)目（2015ZX09501004）；天津市科技計(jì)劃項(xiàng)目（16PTGCCX00090）