缺血后处理对大鼠线粒体功能的影响及在肝脏缺血再灌注损伤中的保护机制  

Effects of ischemia postconditioning on mitochondrial function in rats and its protective mechanisms in hepatic ischemia⁃reperfusion injury

作　　者：李磊 刘晓丹 周凯翔 和林洁 张健 陈强 孟涵 冯欢 张文明 卢骏 周峰 崔洪尊 牛万成 张召辉 LI Lei;LIU Xiaodan;ZHOU Kaixiang;HE Linjie;ZHANG Jian;CHEN Qiang;MENG Han;FENG Huan;ZHANG Wenming;LU Jun;ZHOU Feng;CUI Hongzun;NIU Wancheng;ZHANG Zhaohui(General Surgery Department of the Affiliated Huaihai Hospital of Xuzhou Medical University,Xuzhou 221004,China;State Key Laboratory of Cancer Biology and Department of Physiology and Pathophysiology,Fourth Military Medical University,Xi′an 710032,China)

机构地区：[1]徐州医科大学附属淮海医院普通外科,徐州221004 [2]空军军医大学基础医学院生理与病理生理教研室,西安710032

出　　处：《中国癌症防治杂志》2025年第1期48-54,共7页CHINESE JOURNAL OF ONCOLOGY PREVENTION AND TREATMENT

基　　金：徐州市推动科技创新专项重点研发项目(KC19172)。

摘　　要：目的 探讨肝脏缺血后处理对肝脏线粒体功能的影响,及其在肝脏缺血再灌注损伤(hepatic ischemia reperfusion injury,HIRI)中发挥保护作用的机制。方法 将15只大鼠分为假手术组(Sham组)、缺血再灌注组(IR组)和缺血后处理组(IPO组),每组各5只。Sham组仅行开、关腹操作,IR组使用微血管夹夹闭肝中叶及左叶血管45 min,移去微血管夹开放血管再灌注60 min,IPO组缺血45 min后立即进行3个循环的30 s微血管夹开放及30 s微血管夹夹闭的操作,然后移去微血管夹再灌注60 min。检测3组大鼠血清丙氨酸转氨酶(alanine transaminase,ALT)和天冬氨酸转氨酶(aspartate transaminase,AST)水平,并通过HE染色法观察大鼠肝脏组织病理学改变,进行Suzuki's评分,同时检测三磷酸腺苷(adenosine tripnate,ATP)和细胞内线粒体活性氧(reactive oxygen species,ROS)的相对强度以及细胞膜电位,以评估线粒体功能。结果 与Sham组相比,IR组和IPO组血清ALT水平、AST水平、肝组织病理损伤Suzuki's评分、细胞内线粒体ROS相对强度均显著升高,ATP相对强度及细胞膜电位均降低;与IR组相比,IPO组ALT水平、AST水平、肝组织病理损伤Suzuki's评分、细胞内线粒体ROS相对强度均下降,ATP相对强度及细胞膜电位均升高,差异均有统计学意义(均P<0.05)。Sham组肝组织结构、形态正常,未发现炎性细胞浸润和变性坏死的肝细胞;IR组肝组织中无正常的肝小叶结构,肝细胞出现不同程度的空泡样变,细胞肿胀明显,可见片状细胞坏死、凋亡,肝窦淤血扩张,肝组织中可见炎性细胞聚集和浸润;IPO组肝脏组织病理学改变介于Sham组和IR组之间。结论 肝脏缺血后处理对HIRI具有保护作用,其可能通过调节线粒体功能发挥作用。Objective To investigate the effects of hepatic ischemiapostconditioning on mitochondrial function and its protective mechanism in hepatic ischemia-reperfusion injury(HIRI).Methods A total of 15 rats were divided into the sham surgery group(group Sham),the ischemia-reperfusion group(group IR),and the ischemia postconditioning group(group IPO),with 5 rats in each group.Group Sham only underwent on-off of abdomen.In group IR,the vessels in the middle and left lobes of the liver were clamped by micro-vascular clamp for 45 min,followed by clamp removal and 60 min of reperfusion.And in group IPO,after 45 min of ischemia,3 cycles of 30 s microvascular clip opening and 30 s clamping were performed before60min of reperfusion.Serum levels of alanine transaminase(ALT)and aspartate transaminase(AST)were measured in all three groups of rats.Pathological changes in the liver were assessed by hematoxylin and eosin(HE)staining and evaluated according to Suzuki's scoring system.Adenosine triphosphate(ATP)and intracellular mitochondrial reactive oxygen species(ROS)relative strength,and mitochondrial membrane potential were measured to assess mitochondrial function.Results Compared with Sham group,the levels of ALT,AST,Suzuki′s score of hepatic pathological injury and intracellular mitochondrial ROS relative strength were significantly increased in IR group and IPO group,while the ATP relative strength and mitochondrial membrane potential were decreased(all P<0.05).Compared with group IR,ALT level,AST level,Suzuki′s score of hepatic pathological injury and intracellular mitochondrial ROS relative strength were decreased in group IPO,while ATP relative strength and mitochondrial membrane potential were increased,the differences were statistically significant(all P<0.05).In group Sham,hepatic tis⁃sue exhibited normal structure and morphology,with no significant inflammatory cell infiltration,hepatic degeneration,or necrosis.In contrast,group IR displayed a loss of normal hepatic lobule structure,hepatocytes showed varying degr

关 键 词：肝脏缺血再灌注损伤 缺血后处理 线粒体 

分 类 号：R575.5[医药卫生—消化系统]