Protective effects of continuous norepinephrine infusion in early septic rats / 中国小儿急救医学

ABSTRACT

Objective To investigate the protective effects of continuous norepinephrine infusion and its mechanism in early stage of lipopolysaccharide induced septic rats.Methods Forty SD rats were randomly divided into 5 groups (an external jugular vein catheterization was performed in every rat a day before intraperitoneal injection)saline control group (n =8),endotoxin group (n =8),low dose norepinephrine therepy group(n =8),middle dose norepinephrine therepy group (n =8),and high dose norepinephrine therepy group (n =8).Saline control group received intraperitoneal injection of 0.9％ saline 10 ml/kg,and then received an infusion of 0.9％ saline 1 ml/h.Endotoxin group animals were intraperitoneal injected with lipopolysaccharide 10 mg/kg,and then received an infusion of 0.9％ saline 1 ml/h.Therapy group animals received an infusion of norepinephrine solution 1 ml/h after being intraperitoneal injected LPS 10 mg/kg.The doses of norepinephrine were 0.06,0.3,0.6 μg/(kg· min) respectively.Blood samples were taken 2 h and 6 h later and the levels of serum TNF-α、IL-1β and IL-10 were detected by enzyme-linked immunoadsorbent assay.The membrane potential and three tricarboxylic acid cycle key enzyme activity [isocitrate dehydrogenase(IDH) and pyruvate dehydrogenase (PDH) activity] of isolated liver mitochondrion were detected 24 h later,and the morphologic changes of mitochondria in liver were observed by electronic microscopy.Results In endotoxin group,the levels of serum TNF-α JL-1 β and IL-10 all increased significantly(P ＜ 0.05) and liver mitochondrial membrane potential,PDH and IDH activity decreased significantly compared with control group(P ＜0.05,P ＜0.01).In the middle dose of norepinephrine therepy group,the levels of serum TNF-α and IL-1β all increased significantly (P ＜ 0.05,P ＜ 0.01),the level of serum IL-10 decreased significantly compared with endotoxin group (P ＜ 0.05) ; In the high dose norepinephrine therepy group,the liver mitochondrial membrane potential,PDH and IDH activity increased significantly compared with endotoxin group (P ＜ 0.05).The mitochondrial ultrastructural changes in every group were not obviously.Conclusion In the early stage of septic rats,reversible liver mitochondrion injury can be observed.Norepinephrine infusion can protect early septic rats through attenuating inflammatory reaction and enhancing tricarboxylic acid cycle key enzyme activity and mitochondrial membrane potential level.