失笑散颗粒毒性实验

Study on Shixiaosan Granule on Toxicity in Rats

目的:观察失笑散颗粒对大鼠的毒性。方法:取体质量为140~160 g的雄性SD大鼠30只,随机分成3组,每组10只,分别为A组、B组、C组。正常喂养3 d,给药前禁食10 h,A组给药剂量为65.00 g·kg-1,B组剂量为45.50 g·kg-1,C组剂量为31.85 g·kg-1。给药后观察大鼠的一般状态,包括行为活动、皮毛、分泌物、排泄物、中毒及死亡情况。另取体质量为140~160 g的雄性SD大鼠30只,随机分成两组,分别为实验组和对照组,称质量并记录,给药前禁食10 h,实验组给予最大剂量失笑散颗粒,一次用量64 g·kg-1,每天给药3次,采取灌胃方式给药,此给药剂量相当于临床成人用量的216.5倍。对照组给予等体积的灭菌纯水灌胃。给药2 h后自由饮水和进食,观察时间为2个月,记录观察期末两组大鼠的体质量、饮食及饮水量。观察期结束后,脱颈椎处死大鼠,解剖各组大鼠,肉眼观察其主要脏器是否有病变,并用电子天平测定心、肝、肾、胃、脾的湿质量,计算各脏器系数并记录。对比各组大鼠血液生化指标检测结果。结果:大鼠的一般情况如下,运动情况:第1次给药后,大鼠无明显异常表现,第2次给药后,部分大鼠在2 min后出现整理毛发,自主活动减少,喜静卧不动,第3次给药后,大鼠活动状态同第2次给药后;排泄物及分泌物:第1次给药后2 h,个别大鼠大便较稀,第2次给药后1 h,个别大鼠大便较稀,第3次给药后大鼠状态同第2次给药后,大鼠分泌物无异常,第2天稀便症状基本消失;无中毒及死亡现象。实验结果表明,失笑散的半数致死量无法得出。实验组与对照组给药前后大鼠的体质量、进食量、饮水量无明显变化,且差异无统计学意义(P>0.05);实验组与对照组相比,给药前和给药后大鼠的体质量、进食量、饮水量均无明显变化,且差异均无统计学意义(P>0.05);大鼠的心脏、肝脏、肾脏、肺脏、脾脏的脏器系数均无明显变化,且差异均无统计学意义(P>0.05)。实验组与对照组相比,大鼠的血糖、总胆固醇、三酰甘油均无明显变化,且差异均无统计学意义(P>0.05)。结论:失笑散颗粒剂对实验动物的体质量、进食、饮水及动物脏器无明显不良反应,毒性较小,安全性高,可以为临床用药提供较为可靠的依据。

Objective：To observe and study on toxicity of Shixiaosan Granules in rats. Methods：30 male SD rats weighing 140-160 g were randomly divided into A group,B group and C group,each group of 10 rats. These rats were fed normally for 3 days,before administration of fasting 10 h,A group was given the dose of 65. 00 g·kg^-1,B group was 45. 50 g·kg^-1,C group was 31. 85 g·kg^-1. After administration,the general state of the rats was observed,including behavioral activity,fur,secretion,excretion,poisoning and death. At the same time,30 female SD rats weighing 140-160 g were randomly divided into divided into two groups,the experimental group and the control group,respectively,these rats were weighed and recorded,before administration of fasting 10 h,then the treatment group was administrated Shixiaosan Granules maximum dose of 64 g·kg^-1 by means of intragastric administration,three times a day,the drug dose equivalent to 216. 5 times of clinical dosage of adults. The control group was administrated sterilized water by means of intragastric administration. After 2 hours free drinking and eating,the experimental period was 2months,the weight and diet of each group rats were recorded. The rats were sacrificed by cervical vertebra,the rats were dissected and the main organs of the rats were observed with naked eyes. Results：Rats general situation was as follows,the general status of the rats movement：after the first dose in rats with no obvious abnormality,second times after administration,rats in 2 min after grooming,locomotor activity decreased,like stillness,after the third times of rats and second times after administration the same;excretion and secretion：after the first dose of 2 h,some rats stool was thin,second times after administration of 1 h,some rats stool thin,third rats after administration with the same state after the second dose of rats without abnormal secretions,second days of rare symptoms no poisoning and death phenomenon disappeared. The experimental results showed that Shixiaosan LD50 could not be obtained. The experimental group and the control group to the body weight,food intake,water intake did not change significantly before and after treatment in rats,and the difference was not statistically significant（ P〉0. 05）;the experimental group and control group,before and after administration of rat body weight,food intake,water intake did not change significantly,and the difference was no significant difference（ P〉0. 05）;organ coefficient in rat heart,liver,kidney,lung and spleen had no obvious change,and there was no significant difference（ P〉0. 05）. Compared with the control group,there was no significant change in blood glucose,total cholesterol and three acyl glycerol in the experimental group and the control group（ P〉0. 05）. Conclusion：Shixiaosan Granule on experimental animal body weight,food intake,drinking water and animal organs with no obvious adverse reactions,the drug has less toxicity and high safety,the experiment can provide reliable basis for clinical medication.