复方川芎嗪对动物鼻粘膜及纤毛的毒性研究

Nasal mucosa and mucociliary toxicity study of Compound tetramethylpyrazine

目的:考察川芎嗪单独及与冰片配伍鼻腔给药的鼻纤毛和黏膜毒性。方法:以在体蟾蜍上颚黏膜为纤毛毒性评价的动物模型,考察对蟾蜍上颚纤毛持续摆动时间、纤毛持续运动百分率和蟾蜍上颚黏膜形态的影响。以扫描电镜观察和病理组织切片考察大鼠鼻腔给予川芎嗪(含川芎嗪100mg/ml)和复方川芎嗪(含川芎嗪100mg/ml,冰片10mg/ml)时鼻纤毛毒性和鼻黏膜细胞毒性,并对停药后纤毛和黏膜毒性的可逆性进行研究。结果:在体蟾蜍上颚黏膜的动物试验中,川芎嗪单用组(含川芎嗪100mg/ml)和川芎嗪与冰片伍用组(含川芎嗪100mg/ml,冰片10mg/ml)的蟾蜍上颚黏膜的形态与生理盐水组比较无明显差异。大鼠鼻黏膜纤毛的扫描电镜结果显示川芎嗪单用组和川芎嗪与冰片配伍用组鼻腔给药1w后,鼻纤毛排列稍显杂乱,少数区域有纤毛簇状聚集和脱落现象;病理组织切片显示大鼠鼻黏膜细胞上皮层厚度无明显改变,上皮细胞形状较为规则,未出现毛细血管扩张,但有上皮下区域腺体增生、淋巴细胞浸润等病理表现;停药1w后,扫描电镜观察纤毛受损的情况有所恢复,病理组织切片显示上皮下区域腺体增生及淋巴细胞浸润现象减轻;停药2w后,观察结果和生理盐水组无明显差异。结论:川芎嗪和复方川芎嗪对纤毛和黏膜的毒性轻微且毒性具有可逆性。

Objective： The purpose of this study was aimed at observing Nasal mucosa and mucociliary toxicity byintranasal administration of TMP alone and compatibility with borneol. Methods： In situ toad palate model was established as experimental model to evaluate persistent vibration duration（ PVD）,relative vibration percentage and Mucosal morphology of toad palate ciliary. Scanning electron microscope（ SEM）,mucosa histopathological sections were used to evaluate Nasal cilia toxicity and nasal mucosa cell toxicity of rats which administrated compound TMP and TMP. Reversibility of cilia and mucosal toxicity was more concerned after stopping administration. Results： Toad palate surface form of nasal mucocilia have few difference among physiological saline group,TMP nasal drop group（ with TMP,100 mg / ml） and compound TMP nasal drop group（ with TMP 100 mg / ml,with borneol 10 mg / ml）. Administrated TMP and compound TMP after 1 w,scanning electron microscopy（ sem） results showed thatarrangement of rat nasal mucosa cilia was slightly cluttered,minority areas have cilia cluster aggregation and falls off phenomenon. Pathological biopsy showed the rat nasal mucosa cells in the cortex thickness has no obvious change,shape of epithelial cells are more rules,does not appear the capillaries expansion,but there is epithelial regional gland hyperplasia,lymphocyte infiltration under pathological manifestations. After stopping administration for 1w,the damaged nasal mucocilia recovered,gland hyperplasia and lymphocyte infiltration lessened. After stopping administration for 2w,the result showed that there were no obvious difference with physiologic saline group. Conclutions： Nasal mucosa and mucocilia toxicity of TMP nasal drop and compound TMP nasal drop are not serious toxicity and this toxicity has reversibility.