甘草次酸通过抑制Caspase 3/Bax/Bcl-2凋亡信号通路保护心脏骤停心肺复苏大鼠心脏功能  

Protective Effect of Glycyrrhetinic Acid on Cardiac Function in Rats with Cardiac Arrest/Cardiopulmonary Resuscitation Through Inhibiting Caspase 3/Bax/Bcl-2 Signaling Pathway

作　　者：马汉宁[1] 姬艳燕[2] 陈伟[1] 马磊 杨立山[1] Ma Hanning;Ji Yanyan;Chen Wei;Ma Lei;Yang Lishan(Department of Emergency,General Hospital of Ningxia Medical University,Yinchuan 750004;Operating Room,General Hospital of Ningxia Medical University,Yinchuan 750004)

机构地区：[1]宁夏医科大学总医院急诊科,银川750004 [2]宁夏医科大学总医院手术室,银川750004

出　　处：《中药药理与临床》2019年第4期28-33,共6页Pharmacology and Clinics of Chinese Materia Medica

基　　金：宁夏自然科学基金项目(NZ16269);宁夏科技支撑计划项目(2015)

摘　　要：目的:观察甘草次酸防治心脏骤停心肺复苏(CA/CPR)大鼠心脏功能的作用,并探讨其抑制Caspase 3/Bax/Bcl-2凋亡信号通路分子机制。方法:将60只大鼠随机分为:阴性对照组、模型组、阳性对照组(依达拉奉6 mg/kg)及甘草次酸50、100、200mg/kg剂量组,每天给药1次,连续6 d。实验第7 d,除阴性对照组外,其它各组均采用窒息法建立大鼠CA/CPR模型,并再给予相应药物1次。末次给药后1 h,记录大鼠左室收缩压(LVSP)、左室舒张末期压(LVEDP)、左室内压最大上升速率(+dp/dtmax)、左室内压最大下降速率(-dp/dtmin)及平均动脉压(MABP)等血流动力学参数;采用生化法测定血清LDH、CK及CK-MB含量的变化;取大鼠心尖组织,进行HE病理切片染色,镜下观察心肌组织病理学变化;采用生化法检测大鼠心肌组织SOD、MDA、GSH-Px及T-AOC水平;采用逆转录聚合酶联反应(RT-PCR)及Western blot法检测大鼠心肌组织Caspase 3、Bax及Bcl-2 mRNA和蛋白表达水平。结果:与阴性对照组比较,模型组大鼠LVEDP升高,+dp/dtmax、-dp/dtmin、LVSP及MABP降低,血清LDH、CK及CK-MB含量明显升高;心肌组织SOD、GSH-Px及T-AOC含量降低,MDA含量明显增多;心肌组织肌纤维走行紊乱,有纤维化和断裂现象,部分细胞结构受损、变性或坏死,可见少量炎性细胞浸润,且Caspase 3、Bax mRNA和蛋白表达水平明显上调,Bcl-2 mRNA表达水平明显下调。与模型组比较,甘草次酸200 mg/kg组大鼠LVEDP降低,+dp/dtmax、-dp/dtmin、LVSP及MABP升高,血清LDH、CK及CK-MB活性下降;心肌组织SOD、GSH-Px及T-AOC含量明显升高,MDA含量明显下降;心肌组织病理损伤明显减轻,且Caspase 3、Bax mRNA和蛋白表达水平下调,Bcl-2 mRNA和蛋白表达水平上调。结论:甘草次酸对CA/CPR大鼠心脏功能具有保护作用,其作用机制与抑制氧化应激和下调Caspase 3/Bax/Bcl-2凋亡信号通路有关。Objective : To observe the protection of glycyrrhetinic acid (GA) on rats with cardiac arrest/cardiopulmonary resuscitation (CA/CPR),and to explore its mechanism on inhibiting Caspase 3/Bax/Bcl-2 signaling pathway. Methods: 60 rats were randomly divided into 6 groups:the negative control group,the model group,the positive control group (Edaravone,6 mg/kg) and 200,100,50 mg/kg GA groups. All rats were given corresponding drugs once a day for 6 successive days. On the 7 th day of the experiment,expect for the negative control group,the animal of CA/CPR model was established by asphyxia,and drugs were given one more time. 1 h after the last administration,the left ventricular systolic pressure (LVSP),left ventricular end-diastolic pressure (LVEDP),maximal rise rate of left intraventricular pressure (+ dp/dt max),maximal decreasing rate of left ventricular pressure(-dp/dt min) and the mean arterial blood pressure (MABP) were recorded.The levels of LDH,CK and CK-MB in serum were detected by biochemical method,pathological changes of left ventricular apex tissue were observed by HE staining,the levels of SOD,MDA,GSH-Px and T-AOC in myocardial tissue of mice were detected by biochemical method,the expression levels of Caspase 3,Bax and Bcl-2 mRNA and protein in myocardial tissue of mice were determined by RT-PCR and Western bolt. Results: Compared with the negative control group,LVEDP was increased in the model group,+ dp/dt max,-dp/dt min,LVSP and MABP were decreased,the serum contents of LDH,CK and CK-MB activities were significantly increased,the levels of SOD,GSH-Px and T-AOC in myocardial tissues were decreased,the content of MDA was increased. The myofibrils of myocardial tissues were disordered,with fibrosis and rupture symptom,some cells were found damaged,degenerated or necrotic,and infiltration was observed in inflammatory cells,the expression levels of Caspase 3 and Bax mRNA and protein in myocardial tissues were up-regulated,while Bcl-2 was down-regulated.Compared with the model group,in 200 mg/kg GA group,L

关 键 词：甘草次酸 心脏骤停 心肺复苏 心脏功能 氧化应激 CASPASE 3/Bax/Bcl-2 

分 类 号：R28[医药卫生—中药学]