目的 :探讨独活香豆素(total coumarine of Angelica pubescentis,TCA)处理对APP/PS1双转基因阿尔茨海默模型小鼠的神经保护作用。方法:将7月龄的APP/PS1双转基因小鼠随机分为模型组、独活香豆素高(14.4 mg/kg)、中(7.2 mg/kg)、低剂量组(3.6 mg/kg),每组10只。药物处理后,采用HE染色、尼氏染色检测独活香豆素对阿尔茨海默模型小鼠脑内椎体细胞和尼氏体的影响,用免疫荧光组织化学法观察脑内神经元的变化,并采用Hoechst33258染色观察神经细胞凋亡。结果:病理学观察结果显示:独活香豆素(14.4 mg/kg)组较阿尔茨海默模型组的小鼠椎体细胞数增加(77.56±5.82个/mm2),并且尼氏体数量增加;免疫荧光组化结果显示独活香豆素(14.4 mg/kg)组小鼠脑内海马区中分子量神经丝蛋白荧光强度(83.25±10.74%)明显高于模型组(26.28±3.08%);同时,独活香豆素(14.4 mg/kg)组显著减少凋亡细胞数(14.08±3.27%)。结论:独活香豆素14.4 mg/kg能够减少阿尔茨海默模型小鼠脑内神经性损伤,是通过增强中分子量神经丝蛋白表达和减少细胞凋亡。
Objective: To investigate whether total coumarine of Angelica pubescentis( TCA) exert neuroprotective effect on APP / PS1 double transgenic mice. Methods: 7-month old APP / PS1 mice were randomly divided into model group,TCA low,medium,high dose groups( 3. 6,7. 2,14. 4 mg / kg)( n = 10),with age-matched C57 BL /6J mice of the same genetic background as normal control group. Immunohistochemical fluorescence,HE and Nissl staining as well as Hoechst 33258 staining were used in the present study. Results: In TCA high dose( 14.4 mg / kg) mice,the pyramidal cells in CA3 zone were significantly improved( 77. 56 ± 5. 82 n / mm2,P 〈 0. 01 vs. model group) and Nissl body quantity were increased. In addition,the fluorescence intensity of NF-M was rescued( 83. 25 ± 10. 74%,P 〈 0. 01 vs. model group)and the percentage of apoptosis cells was decreased( 14. 08 ± 3. 27 %,P 〈 0. 01 vs. model group) in TCA high dose( 14. 4 mg / kg) group.Conclusion: TCA( 14. 4 mg / kg) was effective dose,which can significantly protect APP / PS1 mice from neural damage probably through improving NF-M expression and reducing the apoptosis cells in the brain of APP / PS1 transgenic mouse.