不同血管活性药物对兔脓毒症休克肝损伤的保护作用

Effects of different vasoactive agents on the livery injury caused by septic shock

目的:评价不同血管活性药物对兔脓毒症休克肝损伤的保护作用。方法:采用盲肠结扎穿孔(cecalligation and puncture,CLP)联合静脉注入内毒素制备脓毒症休克模型。将56只新西兰大白兔随机分为4组:造模组(B组,n=14),以1 ml.kg-1.min-1速率输注林格液进行液体复苏;多巴胺组(C组,n=14),以1 ml.kg-1.min-1速率输注林格液进行液体复苏,持续输注多巴胺3～15μg.kg-1.min-1;去甲肾上腺素组(D组,n=14),以1 ml.kg-1.min-1速率输注林格液进行液体复苏,持续输注去甲肾上腺素0.05～0.5μg.kg-1.min-1;对照组(A组,n=14),动物仅接受剖腹探查术。各组分为3、6 h两个时相点各7只,留取血标本后离心测定各时相点丙氨酸氨基转移酶(ALT)、肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β),并留取肝脏标本作光镜检查。结果:B、C、D组血中ALT、TNF-α和IL-β值在各时相点均明显高于A组(P<0.05);C、D组血清ALT、TNF-α和IL-β值在3、6 h均低于B组,差异有统计学意义(P<0.05);C组3 h血清指标与D组比较差异无统计学意义(P>0.05),而6 h明显高于D组(P<0.05);形态学观察发现C、D组各时相点肝损伤明显轻于B组。结论:脓毒症休克时肝损伤严重,去甲肾上腺素和多巴胺均可以有效缓解脓毒症休克引起的肝损伤,随着感染时间的延长,应用去甲肾上腺素的效果优于多巴胺。

Objective： To evaluate the effects of different vasoactive agents on the liver injury in a rabbit model of septic shock.Methods： A cecal ligation and puncture procedure combined with intravenous injection of Endotoxin was used to make septic shock model.56 New Zealand white rabbits were randomly divided into the model group（group B,n=14）：the Ringer＇s solution was injected with 1ml·kg^-1·min^-1 for fluid resuscitation;the dopamine group（group C,n=14）：the Ringer＇s solution was injected 1ml·kg^-1·min^-1 for fluid resuscitation,and dopamine was continuous injected with 3-15μg·kg-1·min-1;the norepinephrine group（group D,n=14）：the Ringer＇s solution was injected with 1ml·kg-1·min-1 for fluid resuscitation,and norepinephrine was continuous injected with 3-15μg·kg-1·min-1;the control group（group A,n=14）：the rabbits were only accepted laparotomy.7 rabbits from each group were sacrificed 3h and 6h after septic shock,and ALT,TNF-α and IL-1β test were performed from blood samples after centrifugation at each time point.The morphological and ultrastructure changes of liver specimens were also observed in light microscopic.Results：The ALT,TNF-α and IL-1β in groups B,C,D were significantly higher than group A at each time point（P〈0.05）.The results of group C and group D in 3,6h were lower than the corresponding time point in group B（P〈0.05）.The level of ALT,TNF-α and IL-1β in group C had no significantly difference at 3h when compared with group D,but that was significantly higher than Group D at the 6h time point.The pathological and ultrastructure changes were lessened in group C,D than those in group B.Conclusion： Liver is injuried severely in septic shock model.Norepinephrine and dopamine can also be effectively alleviate liver injury caused by septic shock.As the infection time going,the effect of norepinephrine are better than dopamine.