毒理学杂志

目的 2种不同的阳性对照品经家兔股四头肌注射后，观察注射部位肌肉有无刺激性及其刺激强度，为肌肉刺激评价试验的阳性对照设置提供参考。方法 参照《药物刺激性、过敏性和溶血性研究技术指导原则》，设置1.7%乙酸溶液、0.425%乙酸溶液、5%碳酸氢钠注射液和2.5%碳酸氢钠注射液共4个组，采用股四头肌单次注射给予，1 ml/侧，给药后48 h、72 h、7 d和14 d取注射部位肌肉进行组织病理学检查。结果 动物一般情况观察无异常;给药后48 h、72 h、7 d和14 d解剖观察各组动物，左右侧股四头肌肉可见不同程度的充血和坏死刺激反应，反应级为1～5;光学显微镜检显示，0.425%和1.7%乙酸溶液注射部位肌肉可见间质炎细胞浸润、肌细胞变性、坏死为主的病理改变，5%碳酸氢钠注射液可见程度轻微的坏死及间质炎细胞浸润，2.5%碳酸氢钠注射液未见病理改变。结论 0.425%和1.7%的乙酸溶液可对肌肉造成明显损伤、相对稳定且重复性好，为肌肉刺激评价试验的合适阳性对照。

Objective To observe the stimulation and intensity of two different positive control substances injected into the quadriceps femoris muscle of rabbits,and to provide reference for the positive control setting in muscle stimulation evaluation test.Methods According to the " Technical Guidelines for the Study of Drug Irritability,Allergy,and Hemolysis",a total of 4 groups were set up,including 1. 7% acetic acid solution,0. 425% acetic acid solution,5% sodium bicarbonate injection,and 2. 5% sodium bicarbonate injection. A single injection of 1 ml/side was administered to the quadriceps femoris muscle,and the muscles from injection site were taken for histopathological examination at 48 h,72 h,7 d,and 14 d after administration. Results There were no observed abnormalities in the general condition of the animals. Different degrees of congestion and necrosis stimulation reactions were observed in the left and right quadriceps femoris muscles which were extrated from animals on 48 h,72 h,7 d and 14 d treatment,with reaction levels ranging from 1 to 5.Microscopic examination showed that interstitial inflammatory cell infiltration,muscle cell degeneration,and necrosis were the obvious observation in the muscles at the injection site of 0. 425% and 1. 7% acetic acid solution. Slight necrosis and interstitial inflammatory cell infiltration were found in the 5% sodium bicarbonate injection site. There were no pathological change in the 2. 5% sodium bicarbonate injection site. Conclusion 0. 425% and 1. 7% acetic acid solution could cause obvious stimulation to muscle,which were relatively stable and reproducible. So they were suitable positive control for muscle stimulation evaluation test.