白芍总苷预处理对缺血性脑损伤大鼠海马线粒体功能的保护作用研究  

Protective Effect and Mechanism of TGP Pretreatment on Mitochondrial Function in Hippocampus of Rats with Ischemic Brain Injury

作　　者：陈小丽 李红霞[1] 杨磊[1] 徐立 Chen Xiaoli;Li Hongxia;Yang Lei;Xu Li(No.906 Hospital of Joint Services Force of PLA,Zhejiang,Ningbo 315040,China)

机构地区：[1]中国人民解放军联勤保障部队第九○六医院,浙江宁波315040

出　　处：《中国中医急症》2020年第3期437-440,共4页Journal of Emergency in Traditional Chinese Medicine

基　　金：浙江省宁波市自然科学基金项目(2018A610415)。

摘　　要：目的观察白芍总苷预处理对缺血性脑损伤大鼠缺血侧海马线粒体功能的保护作用,探讨其可能的作用机制。方法采用阻断大脑右侧中动脉的方法复制缺血性脑损伤大鼠模型。设假手术组,模型组,白芍总苷低、中、高[50、100、200 mg/(kg·d)]剂量预处理组和尼莫地平1 mg/(kg·d)预处理组,术前7 d开始灌胃给药。术后24 h取海马线粒体,改良Clark氧电极法测定线粒体呼吸功能,比色法测定ATP含量,原子化学发光法测定游离Ca^2+浓度;透射电子显微镜(TEM)下观察线粒体超微形态变化;比色法测定线粒体肿胀程度,荧光偏振度法测定线粒体膜流动性,测定膜总磷脂含量、膜通透性转换孔(MPTP)开放度、膜电位(△ψm)。结果与模型组比较,经白芍总苷中、高剂量预处理或尼莫地平预处理能够明显抑制缺血性脑损伤大鼠海马区线粒体呼吸功能的降低和ATP含量降低(P<0.01),抑制游离Ca^2+浓度升高(P<0.05),抑制线粒体超微结构病变;缓解线粒体膜肿胀并抑制膜流动性,抑制膜磷脂含量降低(P<0.05或P<0.01)。结论白芍总苷预处理具有保护缺血性脑损伤大鼠海马线粒体功能的作用,其机制可能与抑制线粒体超微结构病变及保护线粒体膜完整性有关。Objective:To study the protective effect and mechanism of TGP pretreatment on mitochondrial function in hippocampus of the rats with ischemic brain injury.Methods:The model of focal cerebral ischemic was established by blocking the right middle cerebral artery.The sham operation group,model group,TGP low,medium,high[50,100,200 mg/(kg·d)]dose pretreatment group and nimodipine 1 mg/(kg·d)pretreatment group were set up,and the drugs were given at 7 days before operation.24 h after operation,the mitochondria in hippocampus were taken,and modified Clark oxygen electrode method was used to measure mitochondrial respiratory function;mitochondrial ATP content were measured;the content of free Ca^2+ was measured by atomic chemiluminescence;the ultrastructural changes of mitochondria was observation by TEM;the mitochondrial membrane swelling in hippocampus was detected by colorimetric determination;the mitochondrial membrane fluidity was detected with fluorescence polarization method;the total phospholipid content of the membrane,the opening degree of the MPTP and the △ψm were measured.Results:Compared with the model group,TGP medium and high dose pretreatment or nimodipine pretreatment could significantly inhibit the decrease of mitochondrial respiratory function(P<0.05 or P<0.01),the decrease of ATP content(P<0.01)and the increase of mitochondrial free Ca^2+ concentration(P<0.05),improve the ultrastructural pathological changes of ultrastructural,reduce swelling of mitochondrial membrane,and improve membrane fluidity and increase membrane phospholipid content(P<0.05 or P<0.01).Conclusion:TGP preconditioning can protect mitochondrial function in hippocampus of the rats with ischemic brain injury,and its mechanism may be related to the inhibition of mitochondrial ultrastructural lesions and protection of mitochondrial membrane integrity.

关 键 词：缺血性脑损伤 白芍总苷 海马 线粒体功能 膜电位 大鼠 

分 类 号：R285.5[医药卫生—中药学]