吗啡预处理对心力衰竭大鼠p38MAPK信号转导通路的影响  

Impact of morphine preconditioning on p38MAPK signaling pathway in rats with heart failure

作　　者：朱雪莲[1] 韩曦[2] 温禹 耿志海[1] 郭红[1] 辛险峰[1] Zhu Xuelian;Han Xi;Wen Yu;Geng Zhihai;Guo Hong;Xin Xianfeng(Department of Anesthesiology,the First Affiliated Hospital of Jiamusi University,Jiamusi,Heilongjiang 154000,China;School of Basic Medical Sciences,Jiamusi University,Jiamusi,Heilongjiang 154000,China)

机构地区：[1]佳木斯大学附属第一医院麻醉科,黑龙江佳木斯154000 [2]佳木斯大学基础医学院

出　　处：《齐齐哈尔医学院学报》2024年第23期2201-2208,共8页Journal of Qiqihar Medical University

基　　金：黑龙江省教育厅基本科研业务费基础研究项目(2020-KYYWF-0291)。

摘　　要：目的 探讨吗啡预处理对心力衰竭大鼠p38MAPK信号转导通路的影响。方法 选取30只体重200~220 g的SD健康SPF级实验大鼠,适应环境1周后,用盐酸阿霉素(ADR)腹腔注射造模心力衰竭(除对照组给生理盐水外,其余按1.5 ml/kg注射,1次/周,共6周,8 d后左心室短轴缩短率(LVFS)<30%表示模型建立成功)。40只大鼠中,20只造模,10只为正常对照,第8周将造模成功的20只大鼠随机分为模型组和吗啡预处理组,每组各10只,正常对照组和模型组不干预,吗啡预处理组灌注吗啡0.050 mg/kg,输注5 min,停5 min,重复3次。实验完成后,处死大鼠并进行腹腔静脉采血,随后通过离心分离上清液,用ELISA方法测定血浆中的BNP、ET-1和IL-6含量;同时,使用生理记录仪测量左心室的收缩末压(LVSP)、舒张末压(LVEDP),以及其内压的最大上升(+dp/dtmax)和下降(-dp/dtmax)速度;取大鼠心肌组织进行Western blot检测p38MAPK、p-p38MAPK蛋白表达;用RT-PCR检测p38MAPK mRNA的表达。结果 模型组和吗啡预处理组的左心室收缩压(LVSP)明显低于对照组,而左心室舒张末期压力(LVEDP)则高于对照组。左心室内压的最大上升速率(+dp/dtmax)在这两个组中均低于对照组,最大下降速率(-dp/dtmax)则高于对照组。吗啡预处理组的这些指标介于模型组和对照组之间,所有差异均具有统计学意义(P<0.05)。与对照组比较,模型组、吗啡预处理组血清BNP、ET-1和IL-6含量均升高,与模型组比较,吗啡预处理组上述指标降低(P<0.05)。与对照组相比,模型组与吗啡预处理组大鼠心肌组织中p38MAPK、p-p38MAPK的表达显著升高,吗啡预处理组表达介于两组之间,差异有统计学意义(P<0.05)。mRNA表达实验表明,模型组与吗啡处理组的心肌p38MAPK mRNA表达高于正常对照组,模型组高于其他两组,差异有统计学意义(P<0.05)。结论 本研究成功构建了心力衰竭大鼠模型。结果显示,吗啡预处理对部分心功能指标有�Objective To explore the impact of morphine preconditioning on the p38MAPK signaling pathway in rats with heart failure.Methods Thirty healthy SPF-grade SD rats weighing 200~220 g were acclimated for one week.Heart failure was modeled in 20 rats by intraperitoneal injection of doxorubicin hydrochloride(ADR)at a dose of 1.5 ml/kg once per week for six weeks,with successful modeling confirmed by a left ventricular fractional shortening(LVFS)of less than 30%eight days after the final injection.The remaining 10 rats served as the normal control group,receiving saline injections.The 20 rats with confirmed heart failure were randomly divided into two groups:the model group and the morphine preconditioning group,each with 10 rats.The normal control and model groups received no intervention,while the morphine preconditioning group was administered morphine at 0.050 mg/kg,infused for 5 minutes,paused for 5 minutes,and repeated three times.After the experiment,rats were sacrificed,and blood was collected via the abdominal vein.Plasma levels of BNP,ET-1,and IL-6 were measured using ELISA.A physiological recorder measured left ventricular systolic pressure(LVSP),end-diastolic pressure(LVEDP),and the maximum rates of pressure increase(+dp/dtmax)and decrease(-dp/dtmax).Myocardial tissue was collected for Western blot analysis of p38MAPK and p-p38MAPK protein expression and RT-PCR for p38MAPK mRNA expression.Results The model and morphine preconditioning groups showed significantly lower LVSP and higher LVEDP compared to the control group.Both groups also exhibited a decrease in+dp/dtmax and an increase in-dp/dtmax compared to the control group.The morphine preconditioning group's metrics were intermediate between the model and control groups,with all differences being statistically significant(P<0.05).Serum BNP,ET-1,and IL-6 levels were elevated in the model and morphine preconditioning groups compared to the control group,but lower in the morphine preconditioning group than in the model group(P<0.05).Myocardial expression of

关 键 词：吗啡 心力衰竭大鼠 P38MAPK信号转导通路 

分 类 号：R541.6[医药卫生—心血管疾病]