目的 观察雷公藤内酯醇对阿尔茨海默病(AD)模型大鼠海马神经元drebrin和cofilin表达的影响。方法 雄性Sprague-Dawley大鼠60只随机等分成对照组(n=20)、模型组(n=20)和用药组(n=20)。大鼠右侧海马内注射β淀粉样蛋白(Aβ1-40)造模,对照组右侧海马内注射等量生理盐水。用药组在右侧海马注射Aβ1-40后每天腹腔注射雷公藤内酯醇0.4 mg/kg,共15 d。Golgi染色检测各组海马神经元树突棘密度的变化。免疫组化染色和逆转录聚合酶链反应(RT-PCR)检测各组海马神经元drebrin和cofilin表达的变化。结果 用药组大鼠海马神经元树突棘密度高于模型组(P<0.05)。用药组大鼠海马drebrin阳性产物平均光密度较模型组明显升高(P<0.01),cofilin阳性细胞数和平均光密度较模型组减少(P<0.05)。用药组大鼠海马drebrin mRNA表达高于模型组(P<0.05),cofilin mRNA表达明显低于模型组(P<0.01)。结论 雷公藤内酯醇可能通过调节drebrin和cofilin的表达,延缓AD模型大鼠海马神经元树突棘的退化。
Objective To observe the effects of triptolide on drebrin and cofilin expression in the hippocampus of rats with Alzheimer's disease (AD).Methods Sixty male Sprague-Dawley rats were equally divided into control group, model group and triptolide-treated group with 20 cases in each group. The AD model was established with unilateral injection of beta amyloid 1-40 (Aβ1-40) into hippocampus in rats. The control group was established with unilateral injection of normal saline with the same volume into hippocampus in rats. The triptolide-treated group was administered triptolide intraperitoneally, 0.4 mg/kg, once a day, for 15 days after modeling. Spine density of hippocampal neurons was assayed by Golgi staining. Drebrin and cofilin expression of hippocampal neurons was assayed by immunohistochemical staining and reverse transcription polymerase chain reaction (RT-PCR).Results The spine density of hippocampal neurons was higher in the triptolide-treated group than in the model group (P<0.05). The average optical density of drebrin was higher in the triptolide-treated group than in the the model group (P<0.01), while the cell number and average optical density of cofilin were lower (P<0.05). The drebrin mRNA expression was higher in the triptolide-treated group than in the model group (P<0.05), and the cofilin mRNA expression was lower (P<0.01).Conclusion Triptolide may delay the degeneration of dendritic spines in hippocampal neurons of AD rats by regulating the expression of drebrin and cofilin.
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