RSR13对高原大鼠肺冲击伤的保护作用及机制研究  

Protective effect and mechanism of RSR13 on lung blast injury in rats at high altitude

作　　者：何青盈 李悦 文静 向伦理 段家翔 廖先建 易斌 甯交琳 HE Qingying;LI Yue;WEN Jing;XIANG Lunli;DUAN Jiaxiang;LIAO Xianjian;YI Bin;NING Jiaolin(Department of Anesthesiology,First Affiliated Hospital,Army Medical University(Third Military Medical University),Chongqing,400038,China;Department of Nephrology,First Affiliated Hospital,Army Medical University(Third Military Medical University),Chongqing,400038,China)

机构地区：[1]陆军军医大学(第三军医大学)第一附属医院麻醉科,重庆400038 [2]陆军军医大学(第三军医大学)第一附属医院肾内科,重庆400038

出　　处：《陆军军医大学学报》2024年第20期2352-2359,共8页Journal of Army Medical University

摘　　要：目的探究血红蛋白变构剂乙丙昔罗[efaproxiral(RSR13)]对高原地区爆炸冲击波致大鼠肺损伤的影响及其作用机制。方法8周龄SD健康雄性大鼠,共82只,按照随机数字表法分为冲击伤组和RSR13+冲击伤组,RSR13+冲击伤组大鼠在接受冲击前2 h腹腔注射RSR13(150 mg/kg):其中60只大鼠放置在距爆源同侧5 m处,为5 m冲击伤组(n=30)、5 m RSR13+冲击伤组(n=30);16只大鼠放置在距爆源同侧6 m处,6 m冲击伤组(n=8)、6 m RSR13+冲击伤组(n=8),余下6只大鼠为对照组(n=6)。观察距爆源5 m处各组大鼠24 h内生存情况。对距爆源6 m处存活24 h大鼠,采用HE染色与肺损伤病理评分比较各组大鼠肺组织损伤情况,测定大鼠动脉血气;采用比色法检测肺组织谷胱甘肽(glutathione,GSH)、丙二醛(malondialdehyde,MDA)、超氧化物歧化酶(superoxide dismutase,SOD)水平;通过蛋白免疫印迹法检测肺组织中剪切胱天蛋白酶-3(cleaved caspase-3)、闭合蛋白(occludin)的表达水平。结果RSR13预处理可增加高原环境下距爆源5 m处爆炸后即刻存活率[46.7%(冲击伤组)vs 93.3%(RSR13+冲击伤组),P<0.01]和爆炸后1 h存活率[46.7%(冲击伤组)vs 86.7%(RSR13+冲击伤组),P<0.01]。RSR13可降低高原环境下距爆源6 m处大鼠肺损伤病理评分[(13.70±0.78)(冲击伤组)vs(8.27±0.93)(RSR13+冲击伤组),P<0.01]。RSR13对高原环境下肺冲击伤大鼠动脉血气无明显影响(P>0.05),RSR13可增加高原距爆源6 m处大鼠肺组织GSH含量[(22.62±10.88)(冲击伤组)vs(40.27±12.47)(RSR13+冲击伤组)μg/g,P<0.05)、但对MDA含量与SOD活性无明显影响(P>0.05),降低肺组织cleaved caspase-3表达量(P<0.01)、增加occludin表达量(P<0.05)。结论RSR13对高原爆炸冲击波所致大鼠肺损伤具有显著的保护作用,这可能与其增加组织抗氧化能力,减少细胞凋亡和降低肺通气屏障通透性有关。ObjectiveTo investigate the impact and mechanism of efaproxiral(RSR13),a hemoglobin allosteric agent,on lung injury in rats caused by explosion-induced shock waves in plateau areas.MethodsEighty-two healthy male SD rats(8-week-old,transferred from an altitude of 2880 m to 4700 m within 6 h)were randomly divided into blast injury group and RSR13+blast injury group(intraperitoneal injection of 150 mg/kg RSR132 h before explosion).Sixty rats were positioned at 5 m from the explosion source and divided into 5-m blast injury group(n=30)and 5-m RSR13+blast injury group(n=30).Additionally,16 rats were positioned at 6 m from the explosion source and then assigned into 6-m blast injury group(n=8)and 6-m RSR13+blast injury group(n=8).The left 6 rats served as control(n=6).Survival outcomes of each rat group positioned 5 m from the explosion source were observed over a 24-hour period.HE staining was used to evaluate the pathological score of the surviving rats positioned at 6 m from the explosion source in 24 h after explosion,along with arterial blood gas analysis.The contents of glutathione(GSH),malondialdehyde(MDA)and superoxide dismutase(SOD)in the lung tissues were determined by colorimetry.Western blotting was conducted to measure the expression levels of cleaved caspase-3 and occludin in the lung tissue.ResultsRSR13 pretreatment increased the survival rate immediately after explosion(93.3%vs 46.7%,P<0.01)and at 1 h after explosion(86.7%vs 46.7%,P<0.01)in plateau areas of 5 m from the explosion source.At high altitude,RSR13 pretreatment reduced the pathological score of lung injury in rats 6 m away from the explosion source(8.27±0.93 vs 13.70±0.78,P<0.01),but had no significant effect on the results of arterial blood gas analysis in rats with lung blast injury(P>0.05).In addition,RSR13 pretreatment also increased GSH content(40.27±12.47 vs 22.62±10.88μg/g,P<0.05),but showed no obvious effect on MDA content and SOD activity(P>0.05),decreased the protein level of cleaved caspase-3(P<0.01)and increased that of occlu

关 键 词：RSR13 高原地区 爆炸伤 冲击波 肺损伤 

分 类 号：R730.51[医药卫生—肿瘤] R730.53[医药卫生—临床医学] R735.2