脑疏宁胶囊对小鼠的急性和长期毒性实验观察

刘庆义; 张寰; 严云卷; 陈彤; 杨媛; 张梅奎

doi:10.3969/j.issn.2095-5227.2022.12.013

脑疏宁胶囊对小鼠的急性和长期毒性实验观察

Evaluation of acute and long-term toxicity of Naoshuning capsule in mice

摘要

摘要:
背景脑疏宁胶囊是解放军总医院张梅奎主任历经多年临床研究探索出的治疗脑卒中的经验方，其临床疗效确切，不良反应小，适用于缺血性脑卒中急性期及恢复期。前期已完成生产工艺、质量控制体系的研究工作。
目的研究脑疏宁胶囊的急性毒性和长期毒性特点，为临床安全用药提供依据。
方法急性毒性实验将40只昆明种小鼠随机分为两组，雌雄各半，以最大给药量18 g/kg灌胃1次，观察给药后14 d内动物体质量、一般状态及主要脏器外观形态有无异常表现，并记录小鼠中毒表现及死亡情况。长期毒性实验将120只SD大鼠随机分为脑疏宁胶囊低剂量组(1.8 g/kg)、中剂量组(3.6 g/kg)、高剂量组(7.2 g/kg)和0.9%氯化钠注射液组，雌雄各半，连续给药13周，每周检测1次体质量和摄食量，分别在停药后24 h和4周时进行血液学、血液生化、脏器相对质量及组织病理学检测。
结果急性毒性实验显示，在14 d的观察期内动物未见死亡和明显中毒症状，对照组与给药组小鼠体质量无统计学差异(P＞0.05)。长期毒性实验显示，高、中、低剂量组与对照组大鼠体质量、脏器指数差异多数无统计学意义(P＞0.05)，高、中、低剂量组大鼠血液学和血液生化学指标均在文献参考的正常检测参考值范围内。各剂量组未见由药物中毒所导致的脏器组织病理形态学改变。
结论脑疏宁胶囊灌胃给药对小鼠和大鼠均未见明显的中毒反应。

Abstract:
Background Naoshuning capsule is an experienced prescription for the treatment of cerebral apoplexy developed by Zhang Meikui, a chief physician of Chinese PLA General Hospital, after years of clinical research. It has definite clinical efficacy and less side effects, and is suitable for the acute and congruent stage of ischemic stroke. The research of production technology and quality control system has been completed in the early stage.
Objective To investigate the characteristics of the acute toxicity and long-term toxicity of Naoxuning capsule, and provide evidences for its clinical safety.
Methods In the acute toxicity experiment, 40 Kunming mice were randomly divided into two groups (sex in half) and given the maximum dose of 18g/kg once by gavage. The body weight, general state and appearance of main organs of the animals within 14 days after the administration were observed, and the poisoning manifestations and death of the mice were recorded. In the long-term toxicity test, 120 SD rats were randomly divided into low (1.8 g/kg), medium (3.6 g/kg), high (7.2 g/kg) dose group, and normal saline group (sex in half). The drug was administered continuously for 13 weeks, and body quality and food intake were tested and recorded once a week. Hematology, blood biochemistry, relative quality of viscera and histopathology were tested at 24 hours after drug withdrawal and 4 weeks after convalescence.
Results Acute toxicity test showed that no death or obvious poisoning symptoms were observed in the mice during the 14-day observation period, and there was no significant difference in body weight between the control group and the administration group (P＞0.05). Long-term toxicity experiments showed that compared with the control group, there were no statistically significant differences in body weight and organ index (P＞0.05) among the high, medium and low dose groups, and both hematological and blood biochemical indexes were within the normal detection reference range of references. No pathomorphological changes of viscera caused by drug poisoning were observed in each dose group.
Conclusion Naoshuning capsule shows no obvious toxic reaction in mice or rats.

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