摘要
目的 研究重组人脑利钠肽(recombinant human brain natriuretic peptide,rh-BNP)调控丝裂原活化蛋白激酶信号通路(mitogen activated protein kinase pathway,MAPK)通路减轻心肌缺血再灌注(ischemia/reperfusion,I/R)损伤的作用及机制。方法 选择无特定病原体级成年雄性Sprague-Dawley大鼠128只。将大鼠按照随机数字表分为假手术(Sham)组、I/R组、I/R+rh-BNP组、阴性对照腺病毒(negative control adenovirus,AdNC)+Sham组、Ad-NC+I/R组、Ad-NC+I/R+rh-BNP组、p38丝裂原活化蛋白激酶(p38 mitogen-activated protein kinase,p38MAPK)的腺病毒(p38MAPK adenovirus,Ad-p38MAPK)+I/R组、Ad-p38MAPK+I/R+rh-BNP组,每组各16只。采用左冠状动脉前降支结扎的方法建立心肌I/R损伤模型,造模前给予rh-BNP腹腔注射或腺病毒心肌多点注射。再灌注180 min后,检测血清乳酸脱氢酶(lactate dehydrogenase,LDH)和磷酸肌酸激酶同工酶(creatine kinase isoenzyme,CK-MB)的含量,心肌梗死面积,心肌中活性氧簇(reactive oxygen species,ROS)和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)的含量及磷酸化p38MAPK(phosphorylated p38MAPK,pp38MAPK)、磷酸化JNK(phosphorylated JNK,p-JNK)、磷酸化细胞外调节蛋白激酶1/2(phosphorylated extracellular regulated protein kinases 1/2,p-ERK1/2)的表达水平。结果 I/R组血清LDH和CK-MB含量、心肌梗死面积、心肌中TNF-α和ROS含量及p-p38MAPK、p-JNK的表达水平均高于Sham组,p-ERK1/2的表达水平低于Sham组(P<0.05);I/R+rh-BNP组血清LDH和CK-MB含量、心肌梗死面积、心肌中TNF-α和ROS含量及pp38MAPK的表达水平均低于I/R组(P<0.05),p-JNK及p-ERK1/2的表达水平与I/R组比较无差异(P>0.05);Ad-p38MAPK+I/R+rh-BNP组血清LDH和CK-MB含量、心肌梗死面积、心肌中TNF-α和ROS含量及pp38MAPK的表达水平均高于Ad-NC+I/R+rh-BNP组(P<0.05)。结论 rh-BNP具有减轻心肌I/R损伤的作用,该作用与抑制p38MAPK通路、减轻炎症反应及氧化应激反应有关。
Objective To study the effect and mechanism of recombinant human brain natriuretic peptide(rhBNP) in alleviating myocardial ischemia-reperfusion(I/R) injury by regulating mitogen activated protein kinase(MAPK)pathway. Methods A total of 128 adult male Sprague-Dawley(SD) rats with specific pathogen free were selected. The SD rats were divided into groups according to random number table, including, sham operation(Sham) group, I/R group,I/R+rh-BNP group, negative control adenovirus(Ad-NC)+Sham group, Ad-NC+I/R group, Ad-NC+I/R+rh-BNP group,p38 mitogen-activated protein kinase adenovirus(Ad-p38MAPK)+I/R group and Ad-p38MAPK+I/R+rh-BNP group,with 16 SD rats in each group. Myocardial I/R injury model was established by ligation of left anterior descending coronary artery. Before modeling, rh-BNP was injected intraperitoneally or adenovirus was injected into myocardium;180minutes after reperfusion, the contents of lactate dehydrogenase(LDH), creatine kinase isoenzyme(CK-MB) in serum,myocardial infarction size, the contents of reactive oxygen species(ROS), tumor necrosis factor-α(TNF-α) and the expression of phosphorylated p38MAPK(p-p38MAPK), phosphorylated JNK(p-JNK) and phosphorylated extracellular regulated protein kinases 1/2(p-ERK1/2) were detected. Results The contents of LDH, CK-MB, myocardial infarction size, the contents of TNF-α, ROS and the expression of p-p38MAPK and p-JNK in I/R group were higher than those in Sham group, p-ERK1/2 expression level was lower than that in Sham group(P<0.05). The contents of LDH, CK-MB,myocardial infarction size, the contents of TNF-α, ROS and the expression of p-p38MAPK in I/R+rh-BNP group were lower than those in I/R group(P<0.05), the expression of p-JNK and p-ERK1/2 had no significant difference compared with I/R group(P>0.05). The contents of LDH, CK-MB, myocardial infarction size, the contents of TNF-α, ROS and the expression of p-p38MAPK in Ad-p38mapk+I/R+rh-BNP group were higher than those in Ad-NC+I/R-rh-BNP group(P<0.05). Conclusion rh-BNP can alleviate myocardi
作者
杨明
李鲲鹏
宋书田
李国靖
YANG Ming;LI Kunpeng;SONG Shutian;LI Guojing(Department of Cardiothoracic Surgery,Cangzhou Central Hospital,Cangzhou,Hebei 061001,P.R.China)
出处
《华西医学》
CAS
2022年第10期1538-1544,共7页
West China Medical Journal
基金
沧州市科学技术局科技支撑计划项目(151302044)。
关键词
心肌缺血再灌注
重组人脑利钠肽
丝裂原活化蛋白激酶
炎症反应
氧化应激反应
Myocardial ischemia-reperfusion
recombinant human brain natriuretic peptide
mitogen activated protein kinase
inflammatory response
oxidative stress response
