持续去甲肾上腺素输注对早期脓毒症大鼠的保护作用  

Protective effects of continuous norepinephrine infusion in early septic rats

作　　者：吴丹 曾其毅[2] 

机构地区：[1]广州市妇女儿童医疗中心儿科重症监护室,510623 [2]南方医科大学珠江医院,广州510280

出　　处：《中国小儿急救医学》2013年第1期73-77,共5页Chinese Pediatric Emergency Medicine

基　　金：基金项目：广东省科技计划项目（20108031600238）;广州市科学计划项目（2010J-E421）;广州市医药卫生科技重大项目（201102A211007）

摘　　要：目的探讨持续去甲肾上腺素输注对早期脓毒症大鼠是否具有保护作用及其作用机制。方法40只SD大鼠随机分成5组，内毒素组（n=8）：腹腔注射LPS10mg／kg，同时持续泵注生理盐水1ml／h；低剂量去甲肾上腺素干预组（n=8）、中剂量去甲肾上腺素干预组（n=8）和高剂量去甲肾上腺素干预组（n=8）：腹腔注射LPS10mg／kg，同时持续泵注去甲。肾上腺素生理盐水溶液1ml／h，去甲。肾上腺素用量分别为0．06、0．3、0．6μg／（kg·min）；正常对照组（n=8）：腹腔注射与静脉泵注与其他两组等容量的生理盐水。监测各组大鼠腹腔注射LPS或生理盐水后2h和6h的血清肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β和IL-10水平；24h时点分离肝脏线粒体检测肝脏线粒体膜电位及肝脏线粒体三羧酸循环关键酶异柠檬酸脱氢酶（IDH）和线粒体丙酮酸脱氢酶（PDH）的活性，并电镜观察24h肝脏线粒体形态学变化。结果与正常对照组相比，内毒素组在注射LPS后2h和6h，血清TNF-α、IL-1β和IL-10水平显著升高（P〈0．05），24h肝脏线粒体膜电位显著下降（P〈0．05），线粒体IDH活性和PDH活性显著下降（P〈0．05，P〈0．01）；去甲肾上腺素干预组与内毒素组相比，中剂量组血清TNF—α和IL-1β水平显著下降及IL-10水平显著上升（P〈0．05），而高剂量组肝脏线粒体膜电位、IDH活性和PDH活性显著升高（P〈0．05）。各组间肝脏线粒体超微结构改变的差异不明显。结论脓毒症早期大鼠肝脏线粒体存在可逆性损伤；持续去甲肾上腺素输注对早期脓毒症大鼠有明显的保护作用，此保护作用可能与其减轻过度的炎症反应和改善线粒体呼吸功能有关。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 norepinephdne 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 ,IL-1β 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 nore

关 键 词：去甲肾上腺素 内毒素 线粒体 肝脏 大鼠 

分 类 号：R285.5[医药卫生—中药学]