远志皂苷对Aβ_(1-40)诱导的AD大鼠学习记忆功能障碍的保护作用研究

Protective effect of tenuigenin on impaired learning and memory in rats with Aβ_(1-40)-induced AD

目的:考察远志皂苷(TEN)对Aβ1-40诱导阿尔茨海默病(AD)大鼠学习记忆能力的保护作用,探讨其可能的作用机制。方法:将50只健康SD大鼠,随机分为对照组、模型组、TEN低、中、高剂量组(18.5,37.0,74.0 mg·kg-1),采用大鼠右侧海马CA1区注射1μL Aβ1-40建立AD大鼠模型,术后各组进行灌胃治疗30 d。治疗结束后采用Morris水迷宫法观察大鼠的学习记忆能力,流式细胞仪检测海马神经细胞凋亡率,免疫印迹法分析海马神经细胞Bcl-2,Bax,Cyt-c及Caspase-3等凋亡相关蛋白的表达。结果:与模型组相比,TEN各治疗组大鼠学习记忆能力明显改善(P<0.01),海马神经细胞凋亡率显著降低(P<0.01),同时Bax,Cyt-c及Caspase-3蛋白表达水平下降明显,而Bcl-2蛋白表达水平显著升高(P<0.05或0.01)。结论:远志皂苷可能通过调节Bcl-2/Bax的平衡比值,阻止Cyt-c的释放,降低Caspase-3的表达,对抗Aβ诱导的海马神经细胞凋亡,进而改善AD大鼠的学习记忆能力。

Objective： To determine the effect of tenuigenin （TEN） on learning and memory and the possi- ble mechanisms in rat model of AB1-40induced AD. Methods： Healthy SD rats （n = 50） were randomly divided into five groups. AB1-40（ 1 uL） was injected into hippocampus CA1 region to establish AD model. Then, rats were treated with intragastric TEN （18.5, 37.0 and 74.0 rag-kg-l） for 30 days. Learning and memory abilities were assessed by Morris water maze; the apoptotic rates of hippocampal neurons were examined by flow cytometry; the expressions of apoptosis-related proteins （Bcl-2, Bax, Cyt-c and caspase-3） in hippocampal neurons were meas- ured by Western blotting. Results： Compared with AD control, TEN significantly increased the abilities of learning and memory （ P 〈 0.01 ）, reduced apoptotic rate of hippocampus neurons （P 〈 0.01 ）, markedly decreased the levels of Bax, Cyt-c and caspase-3, and increased the expression of Bcl-2 （ P 〈 0.05 or 0.01 ）. Conclusion ： TEN can improve the learning and memory function of AD rats through regulating the ratio between Bax and Bcl-2, bloc- king Cyt-c release, reducing caspase-3 expression and counteracting Al3-induced neuronal apoptosis in the hippo- campus.