依托咪酯预处理对犬肝脏缺血／再灌注损伤时谷丙转氨酶、谷草转氨酶及肝组织内丙二醛、超氧化物歧化酶的影响

Effects of pretreatment with etomidate on the contents of alanine transaminase, aspartate transaminase, malondiaidehyde and superoxide dismutase in dogs with hepatic ischemia/reperfusion injury

目的观察依托咪酯预处理对犬肝脏缺血／再灌注（ischemia／reperfusion，T／R）血浆中谷丙转氨酶（alanine transaminase，ALT），谷草转氨酶（aspartate transaminase，AST）以及肝组织内丙二醛（malondialdehyde，MDA）、超氧化物歧化酶（superoxide dismutase，SOD）的影响，以及通过HE染色光镜下观察肝脏损伤情况。方法20只健康成年杂种犬按完全随机法随机分为4组（每组5只）：假手术组（S组）、I／R组、小剂量依托咪酯预处理组（E1组）、大剂量依托咪酯预处理组（E2组）。S组仅分离肝门不结扎，I/R组、E1组、E2组分别于肝缺血前30min静注生理盐水、0．6mg／kg依托咪酯和1．5mg／kg依托咪酯，建立肝I／R模型，分别于缺血前即刻，缺血30min，再灌注1、2h 4个时间点取血清测ALT、AST值。术毕取肝组织测MDA含量、SOD活性，并HE染色，在光镜下行病理学观察。结果I／R组、E1组、E2组各时间点血清ALT、AST活性均高于S组（P〈0．01），E1组、E2组各时间点血清ALT、AST活性均低于I／R组（P〈0．01），且E2组更显著[再灌注2h：ALT：（2911±89）U／L（I／R组）、（863±95）U/L（E2组）；AST：（2722±103）U／L（I／R组）、（1056±115）U/L（E2组）]。与S组比较，I／R组、E1组、E2组肝组织MDA含量升高（P〈0．01），I／R组肝组织SOD活性降低，E1组、E2组肝组织SOD活性升高；与I／R组比较，E1组、E2组肝组织MDA含量降低、SOD活性升高（P〈0．01），且E2组更显著[MDA：（21．70±2．01）nmol·mg-1prot-1（VR组）、（12．69±1．02）nmol·mg-1prot-1（E2组）、SOD：（191±12）nmol·mg-1prot-1（I／R组）、（634±26）nmol·mg-1prot-1（E2组）]。E1组、E2组肝细胞病理学改变轻于I／R组，且E2组更明显。结论依托咪酯预处理对犬肝脏缺血／再灌注损伤（hepatic ischemia／reperfusion injury，HI／RI）具有明显保护作用，与其抑制脂质过氧化反应有关。且大剂量依托咪酯预处理组的保护作用较确实可靠。

Objective To investigate the effects of pretreatment with etomidate on hepatic injury and the contents of alanine transaminase （ALT）, aspartate transaminase （AST） in plasma and malondialdehyde （MDA）, superoxide dismntase （ SOD ） in hepatic tissue during hepatic ischemia/reperfusion injury（HI/RI） in dogs. Methods 20 adult healthy hybrid canines were randomly divided into 4 groups （n=5）： Sham group （group S）, ischemia/reperfusion group （group I/R）, low dosage of Etomidate group （group E 1, 0.6 mg/kg） and high dosage of Etomidate group （group E2, 1.5 mg/kg）. Canines in all groups were injected Etomidate or NS except group S . The porta hepatis of canines in group S was separated without ligation. The model of HI/RI were established by ligating porta hepatis. The biochemical indicators of ALT and AST in plasma were measured at 4 time points： before blocked, 30 min after ischemis, 1, 2 h after reperfusion. The contents of MDA and activity of SOD in hepatic tissue were also measured. Hepatic tissue was observed with light microscope after operation. Results Compared with group S, group I/R, group E1 and group E2 increased the level of ALT and AST in plasma （P〈0.01）. Compared with group I/R, the level of ALT, AST in group E1 and group E2 decreased significantly（P〈0.01 ）, moreover, group E2 decreased more obviously[Reperfusion 2 h： ALT： （2 911±89） U/L（group I/R）, （ 863 ±95 ） U/L（group E2 ） ; AST： （2 722± 103 ） U/L（group I/R ）, （ 1 056± 115 ） U/L（group E2 ） ]. Compared with group S, group I/R,group E1 and group E2 increased the level of MDA and group I/R decreased the expression level of SOD, group E1 and group E2 increased the level of SOD in hepatic tissue （P〈0.01）. Compared with group I/R, group E1 and group E2 decreased significantly the level of MDA and increased significantly the level of SOD in hepatic tissue （P〈0.01）, and group E2 more obviously[MDA： （21.70±2.01） nmol·mg-1·prot-1 （group I/R）, （12.69±1.02） nmol·mg-1·prot-1 （group E2）, SOD： （191±12） nmol·mg-1 ·prot-1（group I/R）, （634±26） nmol·mg-1·prot-1 （group E2 ）]. Light microscope showed evidently that the pathological changes of hepatic tissue were more slight in group E1 and group E2 than that in group I/R, and group E2 more slight than group E1. Conclusions Pretreatment with etomidate has protective effects on hepatic ischemia reperfusion injury, and it is related to the control lipid peroxidation of etomidate. And the protective effects of high dosage of etomidate （1.5 mg/kg） was more reliable.