洗心汤对快速老化模型小鼠血脑屏障通透性及海马组织P-gp、CB1、CB2蛋白表达的影响  

Effects of Xixin Decoction on Blood-brain Barrier Permeability and Expressions of P-gp,CB1 and CB2 Proteins in Hippocampal Tissue of SAMP8 mice

作　　者：韩欣悦 第五永长[2] 段力琦 赵恩龙 张虎 王亚丽[2] 周源 HAN Xinyue;DIWU Yongchang;DUAN Liqi;ZHAO Enlong;ZHANG Hu;WANG Yali;ZHOU Yuan(The First Clinical College of Medicine,Shaanxi University of Chinese Medicine,Xianyang 712046,China;Shaanxi University of Chinese Medicine,Xianyang 712046,China)

机构地区：[1]陕西中医药大学第一临床医学院,陕西咸阳712046 [2]陕西中医药大学,陕西咸阳712046

出　　处：《中国中医药信息杂志》2024年第2期110-115,共6页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：国家自然科学基金面上项目(82074503);陕西省“特支计划”科技创新领军人才项目(2018年);陕西中医药大学神经退行性疾病中医药防治研究学科创新团队项目(2019-QN05)。

摘　　要：目的观察洗心汤对快速老化模型(SAMP8)小鼠血脑屏障通透性及海马组织P-糖蛋白(P-gp)、大麻素受体1(CB1)和大麻素受体2(CB2)蛋白表达的影响,探讨洗心汤治疗阿尔茨海默病(AD)的可能机制。方法60只SAMP8小鼠随机分为模型组、益生菌组和洗心汤高、中、低剂量组,每组12只,另12只抗快速老化(SAMR1)小鼠作为对照组,各给药组分别予相应药物灌胃10周,对照组和模型组灌胃等体积蒸馏水。Morris水迷宫实验检测小鼠学习记忆能力,伊文思蓝法检测小鼠血脑屏障通透性,ELISA检测血清基质金属蛋白酶9(MMP9)、肿瘤坏死因子(TNF)-α、核因子(NF)-κB含量,Western blot检测海马组织P-gp、CB1、CB2蛋白表达,免疫荧光染色检测海马组织P-gp表达。结果与对照组比较,模型组小鼠学习记忆能力明显降低,脑组织伊文思蓝渗出量明显增加,血清MMP9、TNF-α和NF-κB含量明显增加,海马组织P-gp、CB2蛋白表达明显降低,CB1蛋白表达明显升高,差异有统计学意义(P<0.01,P<0.05);与模型组比较,洗心汤高剂量组小鼠学习记忆能力明显提高,脑组织伊文思蓝渗出量明显减少,血清MMP9、TNF-α和NF-κB含量明显降低,P-gp、CB2蛋白表达明显升高,CB1蛋白表达明显降低,差异有统计学意义(P<0.01,P<0.05)。结论洗心汤可改善AD模型小鼠学习记忆能力,其机制与调节血脑屏障通透性及相关蛋白表达,抑制神经炎症有关。Objective To observe the effects of Xixin Decoction on the blood-brain barrier permeability and the expressions of P-glycoprotein(P-gp),cannabinoid receptor 1(CB1)and cannabinoid receptor 2(CB2)in hippocampal tissue of rapidly aging mice(SAMP8);To explore the possible mechanism of Xixin Decoction in the treatment of Alzheimer disease(AD).Methods Totally 60 SAMP8 mice were randomly divided into model group,probiotics group,and Xixin Decoction high-,medium-and low-dosage groups,with 12 mice in each group,another 12 SAMR1 mice were set as control group.The medicated groups received corresponding drugs by gavage for 10 weeks respectively,while the control group and model group were gavaged with equal volume of distilled water.Morris water maze test was used to detect the learning and memory ability of mice,the blood-brain barrier permeability was detected by Evans blue method,the contents of matrix metalloproteinase 9(MMP9),nuclear factor(NF)-κB and tumor necrosis factorα(TNF-α)in serum were determined by ELISA,the expressions of P-gp,CB1 and CB2 in hippocampal tissue were detected by Western blot,P-gp expression in hippocampal tissue was detected by immunofluorescence staining.Results Compared with the control group,the learning and memory ability of mice in model group significantly decreased,Evans blue exudation in brain tissue significantly increased,the contents of MMP9,TNF-αand NF-κB in serum significantly increased,the expressions of P-gp and CB2 protein significantly decreased,the expression of CB1 protein significantly increased,with statistical significance(P<0.01,P<0.05).Compared with the model group,the learning and memory ability of mice in Xixin Decoction high-dosage group significantly increased,the Evans blue exudation in brain tissue significantly decreased,the contents of MMP9,TNF-αand NF-κB in serum significantly decreased,the protein expressions of P-gp and CB2 significantly increased,and the protein expression of CB1 significantly decreased,with statistical significance(P<0.01,P<0.05).Conc

关 键 词：洗心汤 阿尔茨海默病 血脑屏障 快速老化模型小鼠 

分 类 号：R285.5[医药卫生—中药学]