益肾化浊方对SAMP8小鼠学习记忆能力和海马神经元及相关炎症因子的影响

Effects of Yishen Huazhuo Decoction on Learning and Memory Ability, Hippocampal Neurons and Expressions of Inflammatory Factors in Senescence Accelerated Mouse Prone 8

目的观察益肾化浊方对SAMP8小鼠学习记忆能力和海马CA1区神经元、肿瘤坏死因子-α(TNF-α)、核因子-κB(NF-κB)表达的影响,探讨其可能的作用机制。方法将7月龄SAMP8小鼠随机分为SAMP8组和益肾化浊方低、中、高剂量组,选择SAMR1小鼠作为对照;益肾化浊方低、中、高剂量组分别给予3.12、6.24、12.48 g/kg益肾化浊方药液灌胃,SAMR1组和SAMP8组给予等体积蒸馏水灌胃,每日1次,连续4周;采用Morris水迷宫实验评价小鼠学习记忆能力,尼氏染色观察小鼠海马CA1区神经元变化,免疫组化检测小鼠海马CA1区TNF-α和NF-κB的表达。结果水迷宫实验结果显示,各组小鼠平均游泳速度差异无统计学意义(P>0.05);与SAMR1组比较,SAMP8组小鼠逃避潜伏时间显著增加、穿越平台次数显著减少(P<0.05);与SAMP8组比较,益肾化浊方中剂量组小鼠逃避潜伏时间显著减少、穿越平台次数显著增加(P<0.05)。尼氏染色结果显示,与SAMR1组比较,SAMP8组小鼠海马CA1区神经元数量显著减少(P<0.05);与SAMP8组比较,益肾化浊方中剂量组小鼠海马CA1区神经元数量显著增加(P<0.05)。免疫组化染色结果显示,与SAMR1组比较,SAMP8组小鼠海马CA1区TNF-α和NF-κB表达显著增加(P<0.05);与SAMP8组比较,益肾化浊方中剂量组小鼠海马CA1区TNF-α和NF-κB表达显著减少(P<0.05)。结论中剂量益肾化浊方可有效改善7月龄SAMP8小鼠学习记忆能力,该作用机制可能与其减少海马CA1区神经元丢失、抑制炎症因子TNF-α、NF-κB的表达有关。

Objective To investigate the effects of Yishen Huazhuo Decoction on learning and memory ability,hippocampus neurons,tumor necrosis factor-α(TNF-α)and nuclear factor-κB(NF-κB)of senescence accelerated mouse prone 8(SAMP8)and its possible mechanism.Methods 7-month old SAMP8 mice were randomly divided into SAMP8 group,Yishen Huazhuo Decoction low-,medium-,and high-dosage groups.Senescence accelerated mouse resistant 1(SAMR1)were selected as control group.Mice in Yishen Huazhuo Decoction low-,medium-,and high-dosage groups received 3.12,6.24,12.48 g/kg respectively for gavage.The SAMR1 group and the SAMP8 group were given an equal volume of distilled water once a day for 4 weeks.Morris water maze test was used to evaluate the learning and memory ability of mice.Nissl staining was used to observe the changes of neurons in hippocampal CA1 region of mice,and the expressions of TNF-αand NF-κB in hippocampus of mice was detected by immunohistochemistry.Results The results of water maze test showed that there was no significant difference in the average swimming speed among the groups(P>0.05).Compared with the SAMR1 group,the escape latency of the SAMP8 group significantly increased,and the number of crossing platforms was significantly reduced(P<0.05).Compared with the SAMP8 group,the escape latency of the mice in the Yishen Huazhuo Decoction medium-dosage group was significantly reduced,and the number of crossing platforms significantly increased(P<0.05).Nissl staining showed that the number of neurons in hippocampal CA1 region of SAMP8 group significantly decreased compared with SAMR1 group(P<0.05).Compared with the SAMP8 group,the number of neurons in the hippocampal CA1 region of the Yishen Huazhuo Decoction medium-dosage group significantly increased(P<0.05).Immunohistochemical staining showed that compared with SAMR1 group,the expressions of TNF-αand NF-κB in hippocampal CA1 region of SAMP8 group significantly increased(P<0.05).Compared with the SAMP8 group,the expression of TNF-αand NF-κB in the hippocampal CA1 region of Yishen Huazhuo Decoction medium-dosage group significantly decreased(P<0.05).Conclusion Medium-dose Yishen Huazhuo Decoction can effectively improve the learning and memory ability of 7-month old SAMP8 mice,which may be related to the reduction of neuron loss in hippocampal CA1 region and the inhibition of inflammatory factors TNF-αand NF-κB.