胞外信号调节激酶信号通路在血管钠肽减轻大鼠肝缺血再灌注损伤中的作用  

Protective role of vasonatrin peptide in hepatic ischemia-reperfusion injury in rats through activation of extracellular signal-regulated kinase signaling pathway

作　　者：张馨 朱宇麟[1] 刘畅[1] 朱皓阳 于军 吕毅[3] 赵鸽 Zhang Xin;Zhu Yulin;Liu Chang;Zhu Haoyang;Yu Jun;Lyu Yi;Zhao Ge(Department of Anesthesiology,the First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,China;Department of Clinical Experimental Center,Xi’an International Medical Center Hospital,Xi’an 710100,China;National Local Joint Engineering Research Center for Precision Surgery&Regenerative Medicine,the First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,China)

机构地区：[1]西安交通大学第一附属医院麻醉手术部,西安710061 [2]西安国际医学中心医院临床实验中心,西安710100 [3]西安交通大学第一附属医院精准外科与再生医学国家地方联合工程研究中心,西安710061

出　　处：《中华肝胆外科杂志》2023年第2期124-128,共5页Chinese Journal of Hepatobiliary Surgery

基　　金：国家自然科学基金(81670572);陕西省科技攻关计划(2021SF-018)。

摘　　要：目的评价胞外信号调节激酶(ERK)信号通路在血管钠肽(VNP)减轻大鼠肝缺血再灌注损伤中的作用。方法将20只体重200~250 g的健康雄性SD大鼠分为4组:假手术组(S组)、肝缺血再灌注组(I/R组)、VNP组(V组)、PD98059+VNP组(P+V组),每组5只。大鼠肝热缺血再灌注模型采用动脉夹夹闭肝左叶和肝中叶的肝动脉和门静脉45 min,然后再灌注120 min。V组于缺血前10 min注射VNP,P+V组在给予VNP前20 min注射PD98059,再行VNP给药和缺血再灌注处理。检测血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)含量,以及肝组织匀浆超氧化物歧化酶(SOD)和丙二醛(MDA)含量;观察肝组织病理学变化;采用蛋白印迹法测定磷酸化的ERK (p-ERK)1/2蛋白含量。结果与S组相比,I/R组和P+V组血清ALT[(489.65±11.22)、(333.05±24.77)比(33.78±4.88)U/L]、AST[(651.43±14.99)、(503.18±21.48)比(154.84±12.32)U/L]、TNF-α[(12.83±1.09)、(9.64±0.57)比(2.11±0.11)ng/L]、IL-1β[(7.19±0.62)、(5.12±0.22) 比(1.10±0.49)ng/L]、肝组织匀浆MDA[(8.00±0.88)、(5.60±1.01)比(2.76±1.29)μmol/mg]升高,而SOD [(54.89±10.60)、(68.85±8.33)比(126.10±15.63)nmol/mg]降低,差异具有统计学意义(均P<0.05)。与I/R组相比,V组大鼠血清ALT、AST、TNF-α及IL-1β均降低,差异有统计学意义(均P<0.05)。组织病理学显示,I/R组与P+V组肝组织结构损伤明显加重。与I/R组相比,V组p-ERK1/2蛋白表达增高,差异有统计学意义(P<0.05)。结论 VNP可减轻大鼠肝缺血再灌注损伤,其机制可能与激活p-ERK1/2信号通路减轻肝细胞炎症反应有关。Objective To investigate the protective role of extracellular signal-regulated kinase(ERK)signaling pathway in the process that vasonatrin peptide(VNP)reduces hepatic ischemia-reperfusion injury in rats.Methods Twenty SD rats,weighting 200-250 g,were randomly divided into four groups and each group has five rats.The four groups were sham operation group(S group),ischemia-reperfusion group(I/R group),VNP group(V group)and PD98059+VNP group(P+V group).In the rat model of hepatic warm ischemia and reperfusion,the hepatic artery and portal vein of the left lobe and middle lobe of the liver were clamped with arterial clamp for 45 min followed by reperfusion for 120 min.In the V group,VNP(50μg/kg)was injected 10 minutes before ischemia.In the P+V group,PD98059(2 mg/kg)was injected 20 min before VNP injection followed by VNP administration and I/R treatment.The serum levels of alanine amino transaminase(ALT),aspartate amino transferase(AST),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and the superoxide dismutase(SOD)in liver tissue homogenate and malondialdehyde(MDA)were measured.The histopathology of liver tissue was observed.The contents of p-ERK1/2 were detected by Western blot.Results Compared with S group,in I/R group and P+V group the serum levels of ALT[(489.65±11.22),(333.05±24.77)vs.(33.78±4.88)U/L],AST[(651.43±14.99),(503.18±21.48)vs.(154.84±12.32)U/L],TNF-α[(12.83±1.09),(9.64±0.57)vs.(2.11±0.11)ng/L],IL-1β[(7.19±0.62),(5.12±0.22)vs.(1.10±0.49)ng/L],MDA[(8.00±0.88),(5.60±1.01)vs.(2.76±1.29)μmol/mg]increased,while SOD[(54.89±10.60),(68.85±8.33)vs.(126.10±15.63)nmol/mg]decreased(all P<0.05).The histopathology of liver tissue revealed that liver structure damaged more seriously in I/R group and P+V group.Western blot analysis showed that p-ERK1/2 decreased significantly in I/R group and P+V group.Compared with I/R group,ALT,AST,MDA,TNF-αand IL-1βdecreased significantly and SOD increased significantly in V group(all P<0.05).The histopathology of liver tissue revealed that liver

关 键 词：再灌注损伤 缺血 胞外调节蛋白激酶 血管钠肽 大鼠 

分 类 号：R575[医药卫生—消化系统]