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| 四磨汤口服液SD大鼠长期毒性实验研究 |
| 刘正清,孔卫青,杨 华 |
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| (湖南汉森制药股份有限公司,湖南 益阳,413000;北京昭衍新药研究中心股份有限公司,北京,100176) |
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| 摘要: |
| 目的：观察SD大鼠灌胃四磨汤口服液的长期毒性反应。方法：将120只SD大鼠随机分为四磨汤口服液高、中、低3 个剂量组和辅料对照组,连续灌胃给药13周,恢复期4周,观察各组大鼠实验过程中症状发生情况、体质量、血细胞计数[包括白细胞（WBC）、红细胞（RBC）、血红蛋白（HGB）、红细胞压积（HCT）、平均红细胞体积（MCV）、平均红细胞血红蛋白（MCH）、平均红细胞血红蛋白浓度（MCHC）]、血液生化指标[包括丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、总蛋白（TP）、白蛋白（ALB）、白蛋白/球蛋白（A/G）、直接胆红素（TBil）、尿素氮（BUN）、肌酐（Cre）、总胆固醇（CHO）、三酰甘油（TG）]的变化,并观察停药后各指标的恢复情况。结果：四磨汤口服液高、中、低剂量组实验期间均未出现异常症状。与同期同性别辅料对照组相比,末次给药后次日高剂量组雌性大鼠RBC和HGB指标降低（P<0.05）,其他指标和时间点差异均无统计学意义（P＞0.05）。由于RBC和HGB变化幅度较小,均在正常参考值范围内波动,其他红细胞相关指标也未见异常改变,故认为该变化无重要的毒理学意义。各剂量组雄性大鼠血细胞计数指标均未见统计学差异（P＞0.05）。与同期同性别辅料对照组相比,末次给药后次日,高剂量组雄性大鼠BUN、雌性大鼠Cre降低,雄性大鼠CHO升高;与同期同性别辅料对照组相比,末次给药后次日,中剂量组雄性大鼠CHO升高;恢复期结束后,雄性大鼠TBil升高;与辅料对照组相比,恢复期结束后,雌性动物TG降低;上述指标差异均有统计学意义（P<0.05）。以上指标中,CHO、TBil的升高未见明显的剂量-反应关系,且在正常参考值范围内波动,认为无重要的毒理学意义。BUN、Cre、TG的降低无重要的毒理学意义。结论：本实验未见明显不良反应的剂量为45 g/kg,表明四磨汤口服液安全性高。 |
| 关键词: 四磨汤口服液 SD大鼠 长期毒性实验 实验研究 |
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| Long-term toxicity of Simo decoction oral solution in Sprague-Dawley rats：An experimental study |
| LIU Zhengqing,KONG Weiqing,YANG Hua |
| (Hunan Hansen Pharmaceutical Co.,Ltd.,Yiyang 413000,Hunan,China;JOINN Laboratories (Beijing) Inc.,Beijing 100176,China) |
| Abstract: |
| Objective：To investigate the long-term toxicity of Simo decoction oral solution given by gavage in Sprague-Dawley rats.Methods：A total of 120 Sprague-Dawley rats were randomly divided into high-,middle-,and low-dose Simo decoction oral solution groups and excipient control group.The drugs were given by gavage for 13 consecutive weeks,followed by a recovery stage of 4 weeks.Related symptoms and indices were observed during the experiment,including body weight,blood cell counting [white blood cell count,red blood cell count (RBC),hemoglobin count (HGB),hematocrit,mean corpuscular volume,mean corpuscular hemoglobin,and mean corpuscular hemoglobin concentration],and blood biochemical parameters [alanine aminotransferase,aspartate aminotransferase,total protein,albumin,albumin/globulin ratio,total bilirubin (TBil),blood urea nitrogen (BUN),creatinine (Cre),total cholesterol (CHO),and triglyceride (TG)],and the recovery of these indices after drug withdrawal was also observed.Results：No abnormal symptoms were observed in any group during the experiment.Compared with the female rats in the excipient control group on the next day after last administration,those in the high-dose group had significant reductions in RBC and HGB (P<0.05),but there were no significant differences in other indices at other time points (P>0.05).RBC and HGB fluctuated within the range of normal reference values,and abnormal changes in other indices related to red blood cells were not observed,so the changes in RBC and HGB were considered to have no important toxicological significance.There were no significant differences in blood cell counting parameters between the male rats in these groups (P>0.05).Compared with the male or female rats in the excipient control group on the next day after last administration,the high-dose group had significant reductions in BUN in male rats and Cre in female rats and a significant increase in CHO in male rats (P<0.05);compared with the male or female rats in the excipient control group on the next day after last administration,the middle-dose group had a significant increase in CHO in male rats (P<0.05);after the recovery stage ended,there was an increase in TBil in male rats (P<0.05);compared with the excipient control group after the recovery stage ended,there was a significant reduction in TG in female rats (P<0.05).Among the above indices,the increases in CHO and TBil showed no obvious dose-response relationship,and they fluctuated within the range of normal reference values,which were considered to have no important toxicological significance.The reductions in BUN,Cre,and TG had no important toxicological significance.Conclusion：The dose without obvious adverse reaction is 45 g/kg in this experiment,suggesting that Simo decoction oral solution has good safety. |
| Key words: Simo decoction oral solution Sprague-Dawley rat long-term toxicity experiment experimental study |
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