线粒体三磷酸腺苷敏感钾离子通道在大鼠心肺复苏后急性肾损伤中的作用研究  

Role of mitochondrial ATP-sensitive potassium channel in acute kidney injury following cardiac arrest and cardiopulmonary resuscitation in rats

作　　者：田磊[1] 王世伟 赵立 杨倩[1] 陆晓晔[1] 朱长清[1] 杨伟强[1] TIAN Lei;WANG Shiwei;ZHAO Li;YANG Qian;LU Xiaoye;ZHU Changqing;YANG Weiqiang(Department of Emergency,Renji Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200127,China)

机构地区：[1]上海交通大学医学院附属仁济医院急诊科,上海200127

出　　处：《上海医学》2023年第1期28-33,共6页Shanghai Medical Journal

基　　金：国家自然科学基金(81971803);上海市卫生和计划生育委员会科研课题(20184Y0126)。

摘　　要：目的 探索线粒体ATP敏感钾离子通道(mitoKATP)在大鼠心肺复苏后急性肾损伤(AKI)中的作用。方法 采用窒息法建立大鼠心脏骤停-心肺复苏模型,将50只健康成年雄性Sprague Dawley(SD)大鼠随机分为左西孟旦治疗(levo)组、mitoKATP通道激动(mito)组、肌膜KATP通道激动(sarc)组、空白对照(control)组和假手术(sham)组,每组各10只。levo组采用左西孟旦干预,mito组在左西孟旦干预的基础上予sarcKATP抑制剂HMR-1098处理,sarc组在左西孟旦干预的基础上予mitoKATP抑制剂5-HD处理。心肺复苏6 h后收集5组大鼠样本,检测大鼠血清肌酐(sCr)、尿素氮(BUN)、IL-1β、IL-6和TNF-α水平,H-E染色观察肾脏组织损伤情况,采用分光光度法检测线粒体呼吸链复合物Ⅰ、Ⅱ活性,免疫印迹实验检测凋亡相关蛋白cleaved caspase 3表达水平。结果 与sham组比较,control组大鼠心肺复苏6 h后sCr和BUN水平均显著升高(P值均<0.05)。与control组比较,levo组和mito组sCr、BUN水平均显著降低(P值均<0.05);而sarc组sCr和BUN水平的差异均无统计学意义(P值均>0.05)。与control组比较,levo组和mito组肾小管轻度扩张,管型明显减少;而sarc组大鼠肾组织结构变化与control组相似。levo组和mito组IL-1β、IL-6和TNF-α水平均较control组显著降低(P值均<0.05),而sarc组与control组间的差异均无统计学意义(P值均>0.05)。与sham组比较,control组肾组织cleaved caspase 3相对表达量显著增加(P<0.05);与control组比较,levo组和mito组cleaved caspase 3相对表达量均显著减少(P值均<0.05),而sarc组肾组织cleaved caspase 3相对表达量的差异无统计学意义(P>0.05)。与sham组比较,control组线粒体复合物Ⅰ、Ⅱ活性显著受到抑制(P值均<0.05);与control组比较,levo组和mito组线粒体呼吸链复合物Ⅰ、Ⅱ活性均显著增强(P值均<0.05),而sarc组线粒体呼吸链复合物活性的差异无统计学意义(P值均>0.05)。结论 mitoKATP开放能够抑制炎症�Objective To investigate the effects of mitochondrial ATP-sensitive potassium(mitoKATP) channel on acute kidney injury following cardiac arrest and cardiopulmonary resuscitation. Methods Rat models of asphyxia induced cardiac arrest-resuscitation were established. Fifty healthy adult male Sprague Dawley rats were randomly divided into five groups: levosimendan group, mitoKATP channel opener group, sarcolemmal KATP(sarcKATP) channel opener group, blank control group and sham-operation group(n=10). Levosimendan was used in the former three groups. Moreover, HMR-1098 and 5-HD were applied in the mitoKATP and sarcKATP channel opener groups, respectively. The rats were sacrificed 6 h after cardiopulmonary resuscitation. Serum creatinine(sCr), blood urea nitrogen(BUN), interleukin-1β(IL-1β), interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) were measured. H-E staining was used to identify the degree of kidney damage. The activity of mitochondrial respiratory chain complex Ⅰand Ⅱwas detected by spectrophotometry.Western blot was used to detect the expression of cleaved caspase-3. Results sCr and BUN levels in the blank control group were significantly higher than those in the sham-operation group(both P<0.05). Compared with those in the blank control group, the levels of sCr, BUN, IL-1β, IL-6 and TNF-α were significantly decreased in the levosimendan group and mitoKATP channel opener group(all P<0.05), but had no significant change in the sarcKATP channel opener group(all P>0.05). H-E staining showed renal tubular structure damage in the blank control group and sarcKATP channel opener group, while the tubular damage was significantly improved in the levosimendan group and mitoKATP channel opener group. The expression of cleaved caspase 3 in the blank control group was significantly higher than that in the sham-operation group(P<0.05). Compared with that in the blank control group, the expression of cleaved caspase 3 was down-regulated in the levosimendan group and mitoKATP channel opener group(both P<0.05

关 键 词：心脏停搏 心肺复苏术 急性肾损伤 线粒体三磷酸腺苷敏感钾离子通道 

分 类 号：R692.5[医药卫生—泌尿科学]