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目的通过观察二甲苯致耳肿胀模型小鼠的大脑皮层和海马区的病理改变,探讨不同剂量黄连单味药及其在黄连解毒汤中的脑神经毒性,为临床合理使用黄连提供初步的实验依据。方法黄连(单)1～5组及黄连解毒汤(复)1～5组分别给予含黄连生药3.0、2.25、1.5、0.75、0.3 g.kg-1水煎药液;阳性药组给予阿司匹林0.2 g.kg-1;正常组和模型组给予等体积蒸馏水。均灌胃给药,连续5 d,每日1次。于末次给药后30 min用二甲苯涂抹小鼠左耳造模,脱臼处死后取脑组织置中性固定液中,切片,HE法染色,在显微镜下观察其大脑皮层及海马区病理情况。结果空白组、模型组、阳性药组小鼠大脑皮层和海马均正常;单1～4组中,各组小鼠大脑皮层和海马组织均有不同程度的变性,并随剂量增加而增强;复方给药组中仅1组(3.0g.kg-1)、2组(2.25 g.kg-1)小鼠大脑皮层和海马组织有小灶性轻微变性,其余各组均基本正常。结论黄连按0.75 g.kg-1给药5 d即可造成小鼠脑神经损伤,剂量增大,损伤加重;但在黄连解毒汤中应用则较为安全。
OBJECTIVE: To investigate the pathological changes of cerebral cortex and hippocampus in xylene-induced ear swelling model mice and explore the neurotoxicity of different doses of berberine single herb and its toxicity in Coptis chinensis decoction to provide a preliminary experimental basis for clinical rational use of berberine . Methods Coptis chinensis (single) 1 ~ 5 group and Huanglian Jiedu Decoction (complex) 1 ~ 5 group were treated with 3.0,2.25,1.5,0.75,0.3 g.kg-1 decoction of Rhizoma Coptidis crude drug. The positive drug group was given aspirin 0.2 g.kg-1; normal group and model group were given equal volume of distilled water. All gavage, continuous 5 d, 1 day. The model of left ear was applied with xylene 30 min after the last administration, and the brain tissue was fixed in neutral solution after dislocation. HE staining and HE staining were used to observe the pathological changes in the cerebral cortex and hippocampus. Results The cerebral cortex and hippocampus in the blank group, the model group and the positive drug group were all normal. In the groups of 1 ~ 4, the cerebral cortex and hippocampus of the mice in each group all had different degrees of degeneration and increased with the increase of the dose. Only one group (3.0g.kg-1) and two groups (2.25g.kg-1) of mice in the administration group had slight focal degeneration in the cerebral cortex and hippocampus, and the other groups were almost normal. Conclusion Coptis by 0.75 g.kg-1 for 5 d can cause brain damage in mice, the dose increases, the injury increased; but the application of berberine detoxification soup is more safe.