【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。更多还原

【Abstract】 Objective To reproduce a Kunming murine endotoxin shock model suitable for the anti- endotoxin 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 D- Gal and 580mg/kgLPS for later experiment).The venous blood of the mice were collected for the detection of serum content of TNF-αwith 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 le- thality of mice was 100% in the groups 2,6 and 10(P<0.01).The serum content of TNF-αwas main- tained 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.Con- clusion The Kunming mice showed signs of endotoxin shock after D-galactosamine presensitizing and endo- toxin challenge,and it is suitable for anti-endotoxin pharmaceutical research.更多还原