复方川芎嗪对动物鼻粘膜及纤毛的毒性研究

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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: To investigate the nasal cilia and mucosal toxicity of tetramethylpyrazine alone and in combination with borneol. METHODS: The animal model of ciliary mucociliary toxicity in vivo was used to investigate the effects of toad paw on the mandibular ciliary sustained swing time, the percentage of sustained cilia and the morphology of the toad palate mucosa. The nasal ciliary toxicity and nasal mucosal cytotoxicity were determined by scanning electron microscopy and histopathological sections in rats after intranasal administration of ligustrazine (100mg / ml ligustrazine and ligustrazine 100mg / ml and borneol 10mg / ml) The reversibility of the toxicity of cilia and mucosa after drug withdrawal was studied. Results: In the toad palate mucosa animal test, ligustrazine alone group (including ligustrazine 100mg / ml) and ligustrazine and borneol group (containing ligustrazine 100mg / ml, borneol 10mg / ml) toad palate mucosa No significant difference compared with the saline group. Scanning electron microscopy results of rat nasal mucociliary cilia showed that after tetramethylpyrazine alone group and compatibility group with tetramethylpyrazine and borneol were administered intranasally for 1 w, the arrangement of nasal cilia was a bit messy, with clusters of cilia clustered and shedding in a few areas. Pathological tissue sections The results showed that there was no significant change in the epithelial layer thickness of nasal mucosa in rats. The shape of epithelial cells was regular and there was no telangiectasia but hyperplasia of epithelium and lymphocyte infiltration in subepithelial region. After 1 week, the cilia The damaged condition recovered. The histopathological sections showed that the glandular hyperplasia and lymphocyte infiltration in the subepithelial region were relieved. After stopping for 2 weeks, there was no significant difference between the observation group and the saline group. Conclusion: Tetramethylpyrazine and compound tetramethylpyrazine have mild toxicity and reversibility to cilia and mucosa.
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