黄芪多糖提高脑卒中后抑郁模型大鼠学习能力的实验观察

Experimental Observation on Effect of Astragalus Polysaccharides on Learning Ability in Rats with Post-stroke Depression

目的观察黄芪多糖对脑卒中后抑郁(PSD)模型大鼠学习记忆能力及抑郁样行为的影响并分析机制。方法 Wistar大鼠48只,随机均分为假手术组、抑郁模型组、黄芪多糖低剂量组(200 mg/kg)和高剂量组(400 mg/kg)(n=12)。除假手术组外均构建PSD模型。低剂量组和高剂量组大鼠灌胃给予相应剂量的黄芪多糖,抑郁模型组和假手术组给予相同体积的生理盐水对照,实验时间4周。采用糖水摄取实验及Zero水迷宫分析系统评价大鼠抑郁行为;膜片钳技术记录海马CA1区自发性动作电位(AP)和群峰电位(PS)以评价黄芪多糖对PSD模型大鼠学习能力及行为学的影响;采用双抗体夹心ELISA法检测血清细胞因子白介素-1β(IL-1β)和白介素-6(IL-6)含量;Western blotting检测海马CA1区组织中核转录因子-κB (NF-κB)、过氧化物酶体增殖物激活受体-γ(PPAR-γ)蛋白表达,实时定量-PCR检测NF-κB和PPAR-γ基因表达。结果黄芪多糖低剂量组和高剂量组大鼠糖水摄取量明显增多、逃避潜伏期缩短,越台次数增多;大鼠CA1区AP和PS膜电压及血清IL-1β和IL-6均明显降低,CA1区NF-κB蛋白和NF-κB mRNA低表达,而PPAR-γ蛋白和PPAR-γmRNA明显高表达,与抑郁模型组比差异有统计学意义(P<0.05),且两组组间比较差异有统计学意义(P<0.05)。结论黄芪多糖可减轻PSD模型大鼠抑郁样行为,提高学习记忆能力,其机制可能是通过抑制NF-κB信号通路的激活而降低受其调控的细胞因子IL-1β和IL-6释放、减轻大脑中动脉闭塞(MCAO)后创伤性应激及炎症反应并提高CA1区膜稳定性有关。

Objective The effects of Astragalus polysaccharides on learning and memory ability and depression-like behavior in rats with post-stroke depression(PSD) model were observed and analyzed. Methods Forty-eight Wistar rats were randomly divided into sham operation group,depression model group, astragalus polysaccharide low dose group and high dose group(n=12). PSD models were constructed except for the sham operation group. Rats in the low-dose group and the high-dose group were intragastrically administered with the corresponding dose of Astragalus polysaccharide. The depression model group and the sham operation group were given the same volume of saline as the control, and the 4 groups were all treated for 4 weeks. The edema intake experiment and Zero water maze analysis system were used to evaluate the depression behavior of rats. The patch clamp technique was used to record the spontaneous action potential(AP) and group peak potential(PS) in hippocampal CA1 area to evaluate the learning ability of Astragalus polysaccharides in PSD model rats. Behavioral effects;serum cytokines interleukin-1β(IL-1β) and interleukin-6(IL-6) levels were detected by double antibody sandwich ELISA;nuclear transcription factor-κB(NF-κB) was detected by Western blotting in hippocampal CA1 region Peroxisome proliferatoractivated receptor-gamma(PPAR-γ) protein expression, real-time quantitative(RT-PCR) detection of NF-κB and PPAR-γ gene expression. Results In the low-dose and high-dose groups of Astragalus polysaccharides, the sucrose intake increased significantly, the escape latency was shortened, and the number of crossovers increased. The AP and PS membrane voltages and serum IL-1β and IL-6 levels in CA1 area were significantly decreased. NF-κB protein and NF-κB mRNA were down-regulated in CA1 region, while PPAR-γ protein and PPAR-γ m RNA were highly expressed, and the difference was statistically significant(P<0.05). The difference was statistically significant(P<0.05). Conclusion Astragalus polysaccharide can alleviate the depression-like behavior of PSD model rats and improve learning and memory ability. The mechanism may be to reduce the release of cytokines IL-1β and IL-6 regulated by NF-κB signaling pathway and reduce middle cerebral artery occlusion(MCAO). Traumatic stress and inflammatory response are associated with increased membrane stability in the CA1 region.