目的动态观察内毒素致小鼠肝损伤后不同时间点相关指标的变化特点。方法以腹腔注射内毒素(E.coli O55:B5)10mg/kg制备内毒素肝损伤小鼠模型,分别在给予LPS后2、6、12、24小时记录一般状况并取材,肉眼及光镜观察肝组织的病理变化,赖氏法测定血清丙氨酸氨基转氨酶(ALT)浓度,放射免疫分析法检测血清肿瘤坏死因子(TNFα)和白细胞介素-1β(IL-1β)含量。结果内毒素肝损伤模型组小鼠在给予LPS后30分钟即有症状出现;6小时光镜观察出现明显肝组织病理损伤,12小时损害加重并延至24小时;血清ALT值在12小时达到高峰;血清TNF-α在2小时即达高峰,6小时开始缓慢下降,但直至24小时仍较同时间点正常对照组显著增高(P〈0.01);血清IL-1β则在给予LPS后6小时明显升高(P〈0.05),12小时达高峰(P〈0.01),至24小时即与对照组无显著性差异。结论本模型的肝损伤指标及相关炎症因子的动态变化数据可用于抗内毒素肝损伤药物研究。
Objective To observe changes of relevant data after liver injury of mouse models induced by endotoxin (lipopolysaccharide) at different time points. Methods The mouse liver injury models were induced by intraperitoneal injection of LPS ( 10mg/kg, E. coli O55 : B5 ). At 2, 6, 12, 24 hours after LPS administration, general symptoms were recorded and the blood and liver tissue of mice were taken. Pathological damages of liver tissues were checked with unaided eye and light microscope, respectively. The concentration of alanine ami (ALT) of serum was measured by using Reitman mensurate rating. Serum TNF - α and IL - 1β levels were determined by radio immunoassay. Results The symptoms appeared in endotoxic liver injury model group 30min after LPS administration. The pathological damage on the whole liver was distinct at 24h, but under microscope the pathological histologic changes of liver appeared at 6h and the damage was made more serious from 12h to 24h. The level of Serum ALT got to the peak at 12h and went down at 24h, but it was still higher than that in the normal control group. The peak of serum TNF - was at 2h, then went down slowly at 6h, but the level was significantly higher than that in the normal control group at 24h ( P 〈0.01 ). Serum IL - 113 went up markedly at 6h( P 〈 0.05 ), and it got to the peak at 12h( P 〈 0.01 ), then it decreased to the normal level at 24h. Conclusion Above dynamic data about the endotoxic liver injury mouse model can be considered as studying the effects and mechanisms of anti - endo- toxin drugs.