摘要
目的建立适用于拮抗内毒素/脂多糖(LPS)药物研究的昆明小鼠内毒素性休克模型。方法将不同剂量的D-氨基半乳糖(D-Gal)及LPS先后注射于小鼠腹腔,根据注射药物不同分为1组:等渗盐水(NS)+LPS 80mg/kg;2组:NS+LPS 90mg/kg;3组:D-Gal 500mg/kg+NS;4组:D-Gal 500mg/kg+LPS 25μg/kg;5组:D-Gal 500mg/kg+LPS 50μg/kg;6组:D-Gal 500mg/kg+LPS 250μg/kg;7组:D-Gal 600mg-kg+NS;8组:D-Gal 600mg-kg+LPS 10μg/kg;9组:D-Gal 600mg/kg+LPS 25μg/kg;10组:D-Gal 600mg/kg+LPS 50μg/kg。观察注射后小鼠死亡情况,计算其死亡率。选择死亡率100%的剂量组合刺激小鼠,分为对照组:注射D-Gal 600mg/kg+NS;LPS组:注射D-Gal 600 mg/kg+LPS 50μg/kg。于注射后30、75、120min取小鼠静脉血,检测其血清肿瘤坏死因子α(TNF-α)水平。另取小鼠10只,同前分组,于注射后5h处死,取其肺、肝、小肠行病理学观察。结果2、6、10组小鼠死亡率达100%(P<0.01)。对照组小鼠血清TNF-α含量保持在较低水平;LPS组伤后各时相点TNF-α含量均显著高于对照组(P<0.01),在注射后75min时达高峰(6365±2087)ng/L。LPS组小鼠肺、肝、小肠出现明显炎性反应;对照组仅肝脏有轻微病理改变。结论D-Gal致敏小鼠对LPS的反应符合内毒素性休克的特征,该小鼠模型适用于拮抗LPS的药理学研究。
Objective To reproduce a Kunming murine endotoxin shock model suitable for the antiendotoxin pharmaceutical research. Methods Kunming mice were challenged with an intraperitoneal （ i. p. ） injection of different doses of D-galactosamine （D-Gal） and endotoxin （LPS） and divided into 10 groups： i. e, group 1 [ with injection of isotonic saline solution（NS） and LPS] ; group 2 （ with injection of NS and 90mg/kg LPS） , group 3 （with injection of NS and 500mg/kg D-Gal） , group 4 （ with injection of 500mg/kgD-Gal and 25μg /kg LPS）, group 5 （ with injection of 500mg/kg D-Gal and 50μg/kg LPS） , group 6（ with injection of 500mg/kg D-Gal and 250μg/kg LPS ） , group 7（ with injection of NS and 600mg/ kg D-Gal ） , group 8（＂ with injection of 600mg/kg D-Gal and 10μg/kg LPS） , group 9（ with injection of 600mg/kg D-Gal and 25μg/kg LPS） , group10 （ with injection of 600mg/kg D-Gal and 50μg/kg LPS）. The death of the mice were observed and the mortality rate was recorded at 48 post-injection hour（PIH）. The dose of D-Gal and LPS which caused 100% lethality was chosen for the subsequent experiment to serve as control group （ with injection of NS and 600mg/kg D-Gal ） , LPS group （ with injection of 600mg/kg DGal and 580mg/kgLPS for later experiment） . The venous blood of the mice were collected for the detection of serum content of TNF-α with ELISA method at 30,75 and 120 post-injection minutes（PIM）. The tissues of lung, liver, intestine were also harvested at 5 PIH for the pathological examination. Results The lethality of mice was 100% in the groups 2, 6 and 10（ P 〈 0.01）. The serum content of TNF-α was maintained in a low level in control group, but it increased remarkably in LPS group, and it reached peak at 75 PIM （6365 ± 2087ng/L, P 〈0.01 ）. Obvious inflammatory reaction was observed in the lung, liver and intestine in LPS group, while only mild inflammatory reaction was observed in liver in control group. Conclusion The Kunming mice showed signs of endotoxin shock after D-galactosamine presensitizing and endotoxin challenge, and it is suitable for anti-endotoxin pharmaceutical research.
出处
《中华烧伤杂志》
CAS
CSCD
北大核心
2007年第6期424-427,共4页
Chinese Journal of Burns
基金
全军医药卫生科研基金(01L065)
重庆市科技攻关项目(CSTC
2007AC5013)
