二仙益坤汤对围绝经期模型小鼠学习记忆能力的影响

目的:观察二仙益坤汤对围绝经期模型小鼠学习记忆能力的影响并探讨其作用机制。方法:雌性小鼠摘除卵巢模拟围绝经期,随机分为模型组,乙烯雌酚组(DES,0.1 mg·kg-1),二仙益坤汤高、中、低剂量组(30,15,7.5 g·kg-1),另有假手术组作为对照,各组按相应剂量连续ig给药5周后,采用跳台法和Morris水迷宫实验观察其对围绝经期模型小鼠学习记忆能力的影响,并生化检测血清超氧化物歧化酶(SOD),丙二醛(MDA),脑组织一氧化氮(NO),乙酰胆碱(ACh),脑组织过氧化脂质(LPO),SOD活性和一氧化氮合酶(NOS),胆碱酯酶(AChE)活性,荧光定量PCR法检测海马中Bcl-2相关x蛋白(Bax)及B细胞淋巴瘤/白血病-2(Bcl-2)mRNA的表达。结果:与模型组相比较,给药各组能明显减少跳台实验训练错误次数及测试错误次数,延长潜伏期,Morris水迷宫实验中,二仙益坤汤高、中剂量组小鼠定向航行潜伏期缩短、空间搜索穿越站台次数增加;与模型组相比,给药各组均能提高小鼠血清SOD活性,降低MDA含量;提高脑组织SOD活性及Ach含量,降低LPO和NO水平,并降低AchE和NOS的活性;使模型大鼠海马Bcl-2表达上调,并降低Bax表达,差异均有统计学意义(P0.05,P0.01)。结论:二仙益坤汤对围绝经期模型小鼠具有改善学习记忆能力的作用,其作用机制可能与清除自由基、抗氧化和调节神经递质水平并影响凋亡因子Bax及Bcl-2 mRNA的表达等有关。

Effect of Erxian Yikun Decoction on Learning and Memory Ability of Perimenopausal Model Mice

Objective: To investigate the effect of Erxian Yikun decoction on the ability of learning and memory of perimenopausal female mice. Method: The female mice was ovariectomized to simulate perimenopausal status and then randomly divided into model group, diethylstilbestrol group (DES, 0.1 mg· kg^-1), and Erxian Yikun decoction high, middle land low dose groups(30, 15, 7.5 g· kg^-1). The sham operation group was also established as the control group. The mice were given corresponding drugs for 5 weeks. The effect on the ability of learning and memory in the different groups was investigated by using step down test and Morris water-maze test. The superoxide dismutase(SOD) and malondialdehyde(MDA) level in serum, lipid peroxidase(LPO), nitric oxide(NO) and acetyl choline(ACh) level in brain tissue, as well as the activity of SOD, nitric oxide synthase(NOS) and acetyl choline esterase(AChE) were also detected. Fluorescence quantitative PCR was used to detect Bcl-2 Assaciated x protein(Bax) and B cell lymphoma/lewkmia-2(Bcl-2) mRNA expressions in the hippocampus. Result: Compared with model group, the ability of learning and memory was significantly improved, the SOD activity in serum was increased, and the SOD activity and MDA level was decreased in the different treatment groups (P<0.05, P<0.01). Meanwhile, the ACh level in brain tissue was increased, the AChE activity and LPO level and NO level were also decreased in the treatment groups, and Erxian Yikun decoction activated the Bcl-2 and lowered expressions of Bax (P<0.05, P<0.01). Conclusion: Erxian Yikun decoction has the effect in improving the ability of learning and memory, this mechanism may relate to scavenging free radicals, anti-oxidization and regulating neurotransmitter level and influencing the effect of Bcl-2 and Bax expression.