依达拉奉对家兔失血性休克缺血-再灌注损伤的保护作用

目的 观察兔失血性休克再灌注过程中血浆丙二醛(MDA)、一氧化氮(NO)与超氧化物岐化酶(SOD)水平的动态变化,以及肺脏、肾脏病理改变;并探讨依达拉奉的保护作用.方法 29只家兔全身肝素化后随机分为三组:假手术组(C组,n=7)、失血性休克再灌注组(I/R组,n = 10)和依达拉奉保护组(L/R-edaravone组,n=12).后两组制作失血性休克再灌注模型,在10 min内通过左股动脉放血,维持平均动脉压(MAP)40 mmHg达到60 min.I/R-edar-avone组静脉应用依达拉奉.然后开始复苏,要求在60 min内回输全部失血和等量生理盐水,使MAP维持在失血前70%以上.休克后10 h L/R-edaravone组静脉再次应用依达拉奉.在复苏后20 h处死所有家兔,同时取所有兔的右肺部分组织和右肾部分组织作病理检查.分别测休克前、休克1 h、再灌注后1 h、5 h及20 h血浆MDA、SOD、NO含量.结果 休克前三组动物血浆MDA、NO及SOD含量均无显著统计学差异.休克后I/R组家兔血浆MOA(5.35±0.29)μmol/L及NO(27.75±2.88) μmol/L水平均较C组的(4.44±0.59)μmol/L,(25.01±4.95) μmol/L]要高,而I/R组的SOD水平(194.58±14.42)U/ml 较C组(210.86±24.54)U/ml要低(P均<0.01).复苏后20 h这些变化更加明显,I/R组MDA和NO水平持续增加(5.69±0.24)μmol/L,(28.01±3.10)μmol/L,P<0.05],而SOD水平继续下降(151.83±9.36)U/ml,P<0.05].与I/R组比较,I/R-edaravone组的MDA水平显著降低(3.48±0.23) μmol/L,P<0.01],SOD水平明显升高(195.10±11.87)U/ml,P<0.01].病理检查提示依达拉奉可以减轻肺脏和肾脏病理损害.结论 依达拉奉通过清除自由基,有效减轻失血性休克再灌注过程中重要脏器的损害.

Protective effects of edaravone on ischaemia-reperfusion injury in rabbits with haemorrhagic shock

Objective To investigate the dynamic changes of MDA, NO, SOD and pathologic changes of the lung and kidneyduring repefusion after haemorrhagic shock in rabbits, and to study the protective effects of edaravone during thecourse.Method Totally 29 beparinized (3 mg/kg) rabbits were randomly divided into three groups:tho sham-operatedcontrol group (group C, n = 7), the haemorrhagic shock group (group I/R, n = 10), and the haemorrhagicshock group with edaravone infusion (group I/R-edaravone, n = 12). Rabbits in the latter two groups were bledfrom left arteria cmralis in 10 minutes with MAP maintained at 40 mmHg for 60 minutes, and then group I/R-edar-avone was given edaravone intravenously. After that, resuscitation began:all blood loss was replaced with normalsaline within 60 minutes with MAP at the end ≥ 70% MAP before haemorrhagic shock. Edaravone was reinjectedat 10 hours after shock.All rabbits were killed at 20 h after reperfusion.Plasma nitric oxide(NO), malonyldialde-hyde (MDA) and superoxide dismutase(SOD) in every group were measured before shock,60 minutes after shockaad 1 h, 5 h and 20 h after reperfusien. Part of the right lung and the right kidney tissues were taken from everyrabbit for pathologic examnation after sacrifice.Results There was no significant difference in MDA,NO aad SOD among three groups before shock. A higherlevel of MDA (5.35±0.29 μmol/L), NO(27.75 ±2.88 μmol/L)and lower serum concentration of SOD(194.58±14.42U/ml)could be found in group I/R during haemorrhagic shock,as compared to group C(4.44±0.59 μmol/L,25.01±4.95μmol/L,210.86±24.54U/ml,respectively,P<0.01).At 20 hours after resuscitation,MDA and NO contents continued to increase(5.69±0.24 μmol/L and 28.01±3.10 μmol/L respectively,P<0.05)while SOD contents kept decreasing(151.83±9.36 U/ml,P<0.05)in group I/R.Comparing to group I/R,group I/R-edaravone had significant lower level of MDA(3.48±0.23 μmol/L,P<0.01)and higher concentration of SOD(195.10±11.87U/ml,P<0.01).Edaravone attenuated the pathologic changes in the lung and kidney.Conclusions Edaravone could effectively protect vital organs from reperfusion injury caused by free radicals following haemorrhagic shock by reducing plasma levels of MDA,NO and increasing levels of SOD.