贝母素乙抑制MEK/ERK的磷酸化对新生小鼠柯萨奇B病毒性心肌炎心肌细胞凋亡和炎症水平的影响  

Effects of Peiminine Inhibiting MEK/ERK Phosphorylation on Cardiomyocyte Apoptosis and Inflammation Level in Neonatal Mice with Coxsackie Virus B Myocarditis

作　　者：黄亚萍 肖惠玲 李艳红 李俊杰 Huang Yaping;Xiao Huiling;Li Yanhong;Li Junjie(Department of Pediatrics,Xiangyang Central Hospital,Afiliated Hospital of Hubei University of Arts and Sciences,Xiangyang,Hubei 441000)

机构地区：[1]湖北文理学院附属医院襄阳市中心医院儿科,襄阳441000

出　　处：《中药药理与临床》2020年第1期94-99,共6页Pharmacology and Clinics of Chinese Materia Medica

摘　　要：目的:探究贝母素乙抑制MEK/ERK的磷酸化对新生小鼠柯萨奇B病毒性心肌炎心肌细胞凋亡和炎症水平的影响。方法:48只新生BALB/c小鼠中随机挑8只作正常对照组,剩余小鼠采用柯萨奇B3病毒感染小鼠构建CVB3心肌炎动物模型,建模成功后再随机分为曲美他嗪1 mg/kg阳性对照组、模型对照组和贝母素乙2. 5、5、10 mg/kg组;分别尾静脉注射或者灌胃相应药物,连续处理28 d,1次/d;检测小鼠心脏功能指标(心率HR、左心射血分数LVEF、左心室缩短分数FS、左心室壁厚度LVWT及左心室收缩末期容积LVESV);采用ELISA法检测血清中心损标记物肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、肌红蛋白(Mb)、炎症因子白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)及一氧化氮合酶(i NOS)的含量,HE染色观察心肌损伤情况,RT-PCR和Western blotting检测Caspase-3、Caspase-9、丝裂原活化的细胞外信号调节激酶(MEK)/细胞外调节蛋白激酶(ERK)的磷酸化水平。结果:与正常对照组相比,CVB3模型组小鼠心肌细胞损伤显著,其HR、LVEF、FS、LVWT水平显著降低,心肌组织中炎细胞数、LVESV水平、Mb、CK、CK-MB、IL-6、TNF-α、IL-1β、i NOS含量明显升高,Caspase-3、Caspase-9、MEK及ERK磷酸化水平显著上调(P <0. 05);与CVB3模型组相比,贝母素乙各组小鼠心肌细胞损伤明显减轻,其HR、LVEF、FS、LVWT水平显著升高,心肌组织中炎细胞数、LVESV水平、Mb、CK、CK-MB、IL-6、TNF-α、IL-1β、i NOS含量明显降低,Caspase-3、Caspase-9、MEK及ERK磷酸化水平显著下调(P <0. 05)。结论:贝母素乙可保护柯萨奇B病毒性心肌炎新生小鼠心肌受损,抑制心肌细胞的凋亡,并显著改善其心脏功能,缓解炎症水平,可能与抑制MEK/ERK的磷酸化有关。Objective: To explore effects of peiminine inhibiting MEK/ERK phosphorylation on cardiomyocyte apoptosis and inflammation level in neonatal mice with Coxsackie virus B( CVB) myocarditis. Methods: 8 cases were randomly selected from 48 neonatal BALB/c mice as the control group,the remaining mice were infected with Coxsackie virus B3( CVB3 model group) to construct myocarditis animal models. After successful modeling,they were randomly divided into the positive control group( 1 mg/kg trimetazidine),the model group and peimininegroups( 2. 5、5、10 mg/kg). Mice were administered with corresponding drugs for continuous 28 days,once/day. The cardiac function indexes [heart rate( HR),left ventricular ejection fraction( LVEF),left ventricular shortening fraction( FS),left ventricular wall thickness( LVWT) and left ventricular end-systolic volume( LVESV) ]in each group were detected. The contents of heart damage markers such as serum creatine kinase( CK),creatine kinase isoenzyme( CK-MB) and myoglobin( Mb),inflammatory factor such as interleukin-6( IL-6),tumor necrosis factor α( TNF-α),interleukin-1β( IL-1β) and nitric oxide synthase( i NOS) were detected by ELISA method. HE staining was performed to observe myocardial damages. The caspase-3,caspase-9 and MEK/ERK phosphorylation levels were detected by RT-PCR and Western blotting. Results: Compared with the control group,significant cardiomyocytes damage was observed in CVB3 model group,levels of HR,LVEF,FS and LVWT were significantly decreased( P < 0. 05),the number of inflammatory cells in myocardial tissues,the levels of LVESV,Mb,CK,CK-MB,caspase-3,caspase-9,IL-6,TNF-α,IL-1β,i NOS,MEK and ERK phosphorylation were significantly increased( P < 0. 05). Compared with CVB3 model group,cardiomyocytes damage was significantly alleviated in peiminine group,levels of HR,LVEF,FS and LVWT were significantly increased( P < 0. 05),the number of inflammatory cells in myocardial tissues,the levels of LVESV,Mb,CK,CK-MB,caspase-3,caspase-9,IL-6,TNF-α,IL-1β,i NOS,MEK and ERK p

关 键 词：贝母素乙 柯萨奇B病毒性心肌炎 MEK/ERK 凋亡 炎症反应 

分 类 号：R285.5[医药卫生—中药学]