摘要
目的:探讨当归芍药散介导氧化-炎症通路在老年痴呆大鼠模型神经损伤保护中的机制.方法:72 只大鼠随机分成对照组、模型组、当归芍药散低剂量组(12g/kg)、当归芍药散中剂量组(24g/kg)、当归芍药散高剂量组(36g/kg)和尼莫地平组(20mg/kg),每组 12 只.除对照组外,其余组大鼠均复制老年痴呆模型.建模成功后,当归芍药散不同剂量组和尼莫地平组分别灌胃不同剂量当归芍药散、尼莫地平.其余组灌胃等剂量的生理盐水,连续灌胃4 周.Morris水迷宫实验检测空间学习记忆能力.高效液相色谱-电化学检测法海马组织间液去甲肾上腺素(NE)、多巴胺(DA)、5-羟色胺(5-HT)和 5-羟吲哚乙酸(5-hydroxyindole acetic acid,5-HIAA)水平.Longa 法评估各组大鼠神经功能缺陷.酶联免疫吸附检测脑组织白介素 1β(IL-1β)、白介素 10(IL-10)、肿瘤坏死因子α(TNF-α)、超氧岐化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物(GSH-Px).结果:模型组逃避潜伏期均短于对照组(P<0.05).与模型组相比,当归芍药散不同剂量组和尼莫地平组逃避潜伏期均下降(P<0.05).与对照组相比,模型组大鼠的神经功能缺损评分以及脑组织中TNF-α、IL-1β、IL-6 水平升高(P<0.05).当归芍药不同剂量组和尼莫地平组神经功能缺损评分以及脑组织中TNF-α、IL-1β、IL-6 水平低于模型组(P<0.05).模型组大鼠海马组织间液NE、DA、5-HT、5-HIAA水平以及脑组织SOD和GSH-Px含量均低于对照组,脑组织MDA含量高于对照组(P<0.05).与模型组相比,当归芍药散不同剂量组和尼莫地平组大鼠海马组织间液NE、DA、5-HT、5-HIAA水平以及脑组织SOD和GSH-Px含量均升高,脑组织MDA含量降低(P<0.05).与对照组相比,Nrf2 表达下降,TLR4 和NF-κB表达升高(P<0.05).与模型组相比,当归芍药散不同剂量组和尼莫地平组Nrf2 表达升高,TLR4 和NF-κB表达下降(P<0.05).结论:当归芍药散通过Nrf2/TLR4/NF-κB信号通路发挥降低氧化应激反应、抗炎作用对老年痴呆大鼠神经损伤起到保护作用.
Abstract
Objective To explore the protection mechanism of Danggui Shaoyao Powder on nerve injury in rats with senile de-mentia by mediating oxidation-inflammation pathways.Methods A total of 72 rats were randomly divided into control group,model group,Danggui Shaoyao Powder low-dose group(12g/kg),medium-dose group(24g/kg),high-dose group(36g/kg)and ni-modipine group(20 mg/kg),12 cases in each group.Except control group,models of senile dementia rats were replicated in the other groups.After successful modeling,all Danggui Shaoyao Powder groups and nimodipine group were given intragastric admin-istration of different doses of Danggui Shaoyao Powder and nimodipine,while the other groups were given intragastric administra-tion of the same dose of normal saline for 4 weeks.The spatial learning and memory ability were detected by Morris water maze test.The levels of norepinephrine(NE),dopamine(DA),5-hydroxytryptamine(5-HT)and 5-hydroxyindole acetic acid(5-HIAA)in hippocampal interstitium fluid were detected by high performance liquid chromatography-electrochemical detection.The neurological deficits were evaluated by Longa method.The levels of interleukin-1β(IL-1β),interleukin-10(IL-10),tumor necrosis factor α(TNF-α),superoxide dismutase(SOD),malondialdehyde(MDA)and glutathione peroxidase(GSH-Px)in brain tissues were detected by enzyme-linked immunosorbent assay(ELISA).Results The escape latency in model group was shorter than that in control group(P<0.05).Compared with model group,escape latency was shortened in all Danggui Shaoyao Powder groups and nimodipine group(P<0.05).Compared with control group,score of neurological deficits and levels of TNF-α,IL-1β and IL-6 in brain tissues were increased in model group(P<0.05).The score of neurological deficits and levels of TNF-α,IL-1β and IL-6 in all Danggui Shaoyao Powder groups and nimodipine group were lower than those in model group(P<0.05).The levels of NE,DA,5-HT and 5-HIAA in hippocampal interstitium fluid,and levels of SOD and GSH-Px in brain tissues in model group were lower than those in control group,while MDA level in brain tissues was higher than that in control group(P<0.05).Compared with model group,levels of NE,DA,5-HT and 5-HIAA in hippocampal interstitium fluid,and levels of SOD and GSH-Px in brain tissues were increased,while MDA level in brain tissues was decreased in all Danggui Shaoyao Powder groups and nimodipine group(P<0.05).Compared with control group,expression of Nrf2 was decreased,while expressions of TLR4 and NF-κB were increased in model group(P<0.05).Compared with model group,expression of Nrf2 was increased,while expressions of TLR4 and NF-κB were decreased in all Danggui Shaoyao Powder groups and nimodipine group(P<0.05).Conclusion Danggui Shaoyao Powder can play the roles of reducing oxidative stress response and anti-inflammation by Nrf2/TLR4/NF-κB signaling pathways in rats with senile dementia,and thus protect them from nerve injury.
维普
万方数据