摘要
目的观察高压氧(HBO)对模拟高原急性缺氧条件下脓毒症(SEP)大鼠肝损伤的保护作用。方法 56只雄性SD大鼠,随机选取40只,于低压氧舱中模拟海拔5000m高原环境3d,建立急性缺氧模型,随机分为:高原对照组,高原SEP组,高原SEP+HBO组,高原SEP+头孢吡肟(CEF)组,高原SEP+HBO+CEF组,每组8只。除高原对照组行假手术处理外,其余各高原组均行盲肠结扎穿孔术(CLP)建立SEP大鼠模型,CLP后分别行HBO(2个绝对大气压)或(和)CEF(50mg/kg,腹腔注射)处理。剩余16只大鼠,在平原条件下随机分为平原对照组和平原SEP组,每组8只。各组均在建模24h后径心脏取血后处死,分别取肝组织测定丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性并检测血清中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)水平,光镜下观察肝脏组织学变化。结果与平原对照组(ALT 57.0±6.7U/L,AST 194.6±8.0U/L,MDA 0.95±0.13nmol/mg prot,SOD 74.1±7.8U/mg prot)比较,高原对照组(ALT 76.5±12.2U/L,AST 204.4±11.5U/L,MDA 1.18±0.11nmol/mg prot,SOD 59.5±6.6U/mg prot)的ALT、MDA含量明显升高(P<0.05)。与平原SEP组(ALT 103.6±5.8U/L,AST 218.6±11.0U/L,MDA 1.38±0.14nmol/mgprot,SOD 55.5±6.4U/mg prot)比较,高原SEP组(ALT 142.8±7.2U/L,AST 307.5±11.3U/L,MDA 1.75±0.21nmol/mg prot,SOD 44.5±4.4U/mg prot)的ALT、AST水平及MDA含量均明显升高,SOD活性明显降低(P<0.05);与高原SEP组比较,高原SEP+HBO+CEF组(ALT 81.1±14.2U/L,AST 214.2±16.3U/L,MDA 1.23±0.13nmol/mg prot,SOD 72.4±5.7U/mg prot)中ALT、AST、MDA含量升高,SOD活性下降明显(P<0.05),但高原SEP+HBO组与高原SEP组之间无显著性差异。HE染色观察,各SEP组均可见肝细胞浊肿变性,部分呈空泡样变,伴大量炎性细胞浸润,以高原SEP组肝细胞变性及炎细胞浸润最为明显;各处理组中,高原SEP+HBO组与高原SEP组相比,肝细胞变性及炎细胞浸润改变不明显,高原SEP+CEF+HBO组肝细胞浊肿及炎性细胞浸润减轻最为明显。结论在模拟高原急性缺氧条件下,可加重SEP大鼠的肝损伤;HBO能改善缺氧条件下SEP大鼠的氧化应激损伤,减轻其肝组织的炎症损伤。
Objective To investigate the protective effect of hyperbaric oxygen（HBO） against hepatic injury of septic rats under acute hypoxia of simulated high altitude.Methods Forty rats were randomly selected from 56 male healthy Sprague-Dawley（SD） rats,and the acute hypoxia model was reproduced in the rats by keeping the rats in the low pressure oxygen chamber for 3 days to simulate acute hypoxia of 5000m altitude.The 40 acute hypoxic rats were then randomly divided into 5 groups（8 each）： high altitude control group,high altitude sepsis（SEP） group,high altitude SEP＋HBO group,high altitude SEP＋cefepime（CEF） group and high altitude SEP＋HBO＋CEF group.Sepsis was reproduced by cecal ligation puncture（CLP） in all the acute hypoxic rats except those in high altitude control group.The SEP rats were then treated with HBO（2 atmosphere absolute） or/and CEF（50mg/kg,intraperitoneal injection）.The remaining 16 rats were then randomly divided into plain control group and plain SEP group（8 each）.All animals were sacrificed at 24h after modeling,the liver and blood samples were collected for biochemical and histopathological analysis.The aspartate aminotransferase（AST） and alanine aminotransferase（ALT） levels in blood samples,and the activity of superoxide（SOD） and the contents of malondialdehyde（MDA） were determined.Results The ALT level and MDA content increased significantly（P〈0.05） in high altitude control group（ALT 76.5±12.2 U/L,AST 204.4 11.5 U/L,MDA 1.18±0.11nmol/mg prot,SOD 59.5±6.6 U/mg prot） compared with that in plain control group（ALT 57.0 6.7 U/L,AST 194.6±8.0 U/L,MDA 0.95±0.13nmol/mg prot,SOD 74.1±7.8 U/mg prot）.The ALT and AST levels and MDA content increased significantly,while the SOD activity decreased significantly（P〈0.05） in high altitude SEP group（ALT 142.8±7.2 U/L,AST 307.5±11.3 U/L,MDA 1.75±0.21 nmol/mg prot,SOD 44.5±4.4 U/mg prot） compared with that in plain SEP group（ALT 103.6±5.8 U/L,AST 218.6±11.0 U/L,MDA 1.38±0.14 nmol/mg prot,SOD 55.5±6.4 U/mg prot）.The ALT and AST levels and MDA content increased while the SOD activity decreased in high altitude SEP＋HBO＋CEF group（ALT81.1±14.U/L,AS214.2±16.U/L,MD1.23±0.13 nmol/mg prot,SOD 72.4±5.7 U/mg prot） compared with that in high altitude SEP group（P〈0.05）.No significant difference was found between high altitude SEP group and high altitude SEP＋HBO group.Degeneration of hepatic parenchyma was observed,and vacuolar degeneration was found in a part of hepatic sections,and intensive polymorphonuclear cell infiltration was observed in livers of all the septic animals,especially in those animals of high altitude SEP group.No obvious liver cell degeneration and inflammatory cell infiltration were noted in high altitude SEP group and high altitude SEP＋HBO group.In high altitude SEP＋CEF＋ HBO group,the degree of hepatic cell degeneration and inflammatory cell infiltration were reduced significantly.Conclusions Under acute hypoxia at simulated high altitude condition,hepatic injury is aggrarated in SEP rats;HBO may alleviate the oxidative stress injury and inflammatory injury of the liver in septic rats with hypoxia.
出处
《解放军医学杂志》
CAS
CSCD
北大核心
2011年第2期153-157,共5页
Medical Journal of Chinese People's Liberation Army
基金
全军医药卫生科研项目重大专项课题(08Z012)
关键词
急性缺氧
脓毒症
高压氧
氧化应激
肝
acute hypoxia； sepsis； hyperbaric oxygenation； oxidative stress injury； liver；
