红景天苷对AD模型小鼠大脑线粒体功能和海马细胞增殖的影响

Effects of salidroside on mitochondrial function in the brain and hippocampal cell proliferation in AD model mice

目的:探讨红景天苷对D-半乳糖联合亚硝酸钠注射所致AD模型小鼠大脑组织线粒体功能和海马齿状回细胞增殖的作用。方法:将45只小鼠随机分为正常组、模型组、红景天苷组,每组15只。红景天苷组、模型组小鼠每日腹腔注射亚硝酸钠(50 mg/kg)和皮下注射D-半乳糖(150 mg/kg),连续造模60 d,正常组则进行腹腔和皮下注射等体积生理盐水。造模期间,红景天苷组小鼠同时皮下注射红景天苷(40 mg/kg),正常组和模型组小鼠注射等体积生理盐水。给药结束后,检测小鼠大脑组织线粒体功能和海马齿状回神经干细胞增殖水平。采用JC-1荧光探针检测线粒体膜电位,采用Clark-type氧电极法测定线粒体呼吸控制率(RCR),采用荧光素酶生物化学发光法检测腺苷三磷酸(ATP)含量,以BrdU标记增殖细胞并采用BrdU免疫组化技术检测海马干细胞增殖水平。结果:与正常组比较,模型组小鼠大脑线粒体膜电位水平、RCR和ATP含量明显降低,BrdU阳性细胞计数明显减少,差异有显著性意义(P<0.05);与模型组比较,红景天苷组小鼠大脑线粒体膜电位水平、RCR和ATP含量明显升高,BrdU阳性细胞计数明显增加,差异有显著性意义(P<0.05)。结论:红景天苷对AD模型小鼠脑组织线粒体功能具有一定程度的保护作用,能改善海马齿状回颗粒下层细胞增殖水平,提示其可能具有促进神经发生的作用。

Objective:To explore the effects of salidroside on mitochondrial function in the brain tissue and hippocampal dentate gyrus cell proliferation of AD model mice induced by D-galactose combined with sodium nitrite.Methods:A total of 45 mice were randomly divided into the normal group,model group,and salidroside group,with 15 mice in each group.Mice in the salidroside and model groups received daily intraperitoneal injection of sodium nitrite(50 mg/kg)and subcutaneous injection of D-galactose(150 mg/kg)for 60 days,while the normal group received equivalent volumes of saline via intraperitoneal and subcutaneous injections.During the modeling period,mice in the salidroside group administered subcutaneous injections of salidroside(40 mg/kg),while mice in the normal and model groups received saline injections of equivalent volumes.After administration,mitochondrial function in the brain tissue and proliferation levels of hippocampal dentate gyrus neural stem cells in mice were evaluated.Mitochondrial membrane potential was detected using JC-1 fluorescent probe,respiratory control ratio(RCR)of mitochondria was determined using Clark-type oxygen electrode method,adenosine triphosphate(ATP)content was measured using the luciferase bioluminescence method,and proliferation cells were labeled with BrdU and hippocampal stem cell proliferation levels were assessed using BrdU immunohistochemistry technique.Results:Compared to the normal group,the model group of mice exhibited significantly reduced levels of mitochondrial membrane potential,RCR,and ATP contents,as well as a noticeable decrease in BrdU-positive cell counts,with significant differences(P<0.05).When compared to the model group,the salidroside group of mice showed remarkable increased levels of mitochondrial membrane potential,RCR,and ATP contents,along with a significant increase in BrdU-positive cell counts,demonstrating significant differences(P<0.05).Conclusion:Salidroside exhibits a certain protective effect on mitochondrial function in the brain tissue of AD model mice,while also enhancing the proliferation levels of granule cells in the subgranular zone of the hippocampal dentate gyrus,indicating its potential role in promoting neurogenesis.