康炎净颗粒对大鼠长期毒性试验研究

Chronic toxicity test of Kangyanjing granule in rats

目的观察连续灌胃给予康炎净颗粒对大鼠产生的毒性反应。方法将160只雌性大鼠随机分为空白对照组(对照组)、康炎净颗粒低剂量组(低剂量组,9. 69 g/kg)、康炎净颗粒中剂量组(中剂量组,28. 77g/kg)和康炎净颗粒高剂量组(高剂量组,85. 44 g/kg),每组40只,每天给药1次,连续给药6个月,停药4周,观察给药中、末期及停药恢复期大鼠的一般状况,称量大鼠体重,计算脏器系数,测定主要血液学指标、生化学指标,并进行脏器组织病理学检查。结果高剂量组于给药第1周开始,体重、摄食量均明显低于空白对照组,并在12周出现死亡现象。给药3个月后,高剂量组大鼠红细胞计数、血红蛋白、红细胞压积、肌酐明显低于对照组(P <0. 05);平均血细胞容积、网织红细胞百分率、白细胞计数、中性粒细胞比率,血清尿素氮、血清钾,肝、脾、肾、肾上腺脏器指数明显高于对照组(P <0. 05)。给药6个月后,高剂量组大鼠红细胞计数、血红蛋白、红细胞压积、肌酸激酶明显低于对照组(P <0. 05),平均血细胞容积,平均血红蛋白含量,网织红细胞百分率,肝、脾、肾脏器指数明显高于对照组。停药4周后,高剂量组大鼠红细胞计数、血红蛋白、红细胞压积明显低于空白对照组(P <0. 05);网织红细胞百分率,肝、脾、肾脏器指数明显高于对照组(P <0. 05)。结论康炎净颗粒大鼠灌胃给药安全剂量为28. 77 g/kg以下,约为临床成人拟用量的22. 27倍(成人按60 kg计)。

Objective To observe the chronic toxicity of Kangyanjing granule in rats with long-term adminis-tration. Methods Totally 160 female rats were randomly divided into 4 groupsblank control group （ control group） and Kangyanjing granule low-dose（9. 69 g/kg） , medium-dose（28. 77 g /k g ） and high-dose（85. 44 g /kg ） groups, with 40 rats in each group. Each group was intragastrically administered with drugs once a day for consecutively 6 months, and then drugs were stopped for 4 weeks for observation. The general condition was observed,body weight was recor-ded , hematology indexes and biochemical indicators were determined,the major organ coefficient was calculated,and histological examination was performed in the middle and late stages of drug administration and after stopping drugs. Results The body weight and the food intake of rats in high-dose group were significantly lower than those of control group at the beginning of first week and there was rat death in 12 weeks （P 〈0. 0 5 ） . After 3 months o f administration, the erythrocyte count, hemoglobin, hematocrit and creatinine in high-dose group were significantly lower than those in control group （ P 〈0.05） ;the mean corpuscular volume,reticulocyte percentage,leukocyte count,neutrocyte counts, se- rum urea nitrogen, serum potassium, liver in d ex, spleen index, kidney index and adrenal index were significantly higher than those of control group （ P 〈 0.05）. After 6 months of administration,the red blood cell count,hemoglobin and hematocrit and creatine kinase of high-dose group were significantly lower than those of control group （ P 〈 0.05 ）, while mean corpuscular volume, mean hemoglobin, reticulocyte percentage, liver indexes, spleen indexes and kidney in-dexes were significantly higher. After 4 weeks of withdrawal, the red blood cell count, hemoglobin and hematocrit in high-dose group were significantly lower than those of control group （ P 〈 0.05）,while reticulocyte percentage,liver index,spleen index,and kidney index were significantly higher than those of control group （ P 〈0.05）. Conclusion The safe dose of Kangyanjing granule given to rat is under 28. 77 g/kg,which is equivalent to 22. 27 times of clinical dosage for adults （according to 60 kg body weight of adult）.