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目的 比较LPS、BCG +LPS诱导的免疫性肝损伤模型的特点及肝中cAMP的变化 ,以建立合适的动物模型 ,并为药物作用及肝损伤机制探讨提供参考。方法 昆明种小鼠 ,分为 5组 :①对照组 ;②BCG组 (ip 1mg·kg- 1 BCG ,7d后处理动物 ) ;③LPS 0 2mg ;④LPS 0 4mg组 (分别ip 0 2 ,0 4mg·kg- 1 ,6h后处理动物 ) ;⑤BCG +LPS组 (ip 1mg·kg- 1 BCG 7d后ip 0 2mg·kg- 1 LPS 6h后处理动物 )。取血清 ,测定ALT、GST活性 ;HE染色 ,光镜观察组织损伤情况 ;制备肝匀浆 ,放射免疫法测定cAMP含量。结果 组织学检查表明 ,给予BCG或LPS均能引起中性粒细胞浸润。单独给予BCG或 0 2mg·kg- 1 LPS未见明显的肝组织损害 ,但经BCG预处理后 ,0 2mg·kg- 1 LPS可使血清ALT、GST水平显著增高。单独给予 0 4mg·kg- 1 LPS也能引起明显的肝组织损伤。经BCG预处理后的小鼠肝组织内cAMP含量明显下降 ,而单独LPS刺激 ,则使肝内cAMP含量呈剂量依赖性增高。结论 LPS、BCG +LPS均能引起典型的免疫性肝损伤 ,经BCG预处理 ,能增强内毒素刺激诱导的肝脏毒性。不同的免疫性肝损伤模型所致肝内cAMP含量的变化不同 ,在进行机制研究及药物药理作用研究时应予以考虑
Objective To compare the characteristics of cAMP in liver induced by LPS and BCG + LPS and to establish a suitable animal model to provide reference for the drug action and the mechanism of liver injury. Methods Kunming mice were divided into 5 groups: ① control group; ② BCG group (ip 1 mg · kg -1 BCG, 7 days after treatment); ③ LPS 0 2 mg; ④ LPS 0 4 mg group (ip 0 2, 0 4 mg · kg - 1, 6h post-treatment of animals); ⑤ BCG + LPS group (ip 1mg · kg-1 BCG 7d after ip 0 2mg · kg-1 LPS 6h after treatment of animals). The serum was collected to measure the activity of ALT and GST. HE staining and light microscopy were used to observe the tissue damage. The liver homogenate was prepared and cAMP content was determined by radioimmunoassay. Results Histological examination showed that neutrophil infiltration could be induced by BCG or LPS administration. BCG alone or 0 2mg · kg-1 LPS alone showed no significant liver damage, but after BCG pretreatment, 0.2mg · kg-1 LPS could significantly increase serum ALT and GST levels. Administration of 0 4 mg · kg -1 LPS alone also caused significant hepatic tissue damage. The cAMP content in the liver of the mice pretreated with BCG decreased significantly, but LPS stimulation alone increased the intra-hepatic cAMP content in a dose-dependent manner. Conclusions Both LPS and BCG + LPS can cause typical immune liver injury. Pretreatment with BCG can enhance liver toxicity induced by endotoxin stimulation. Different immunological liver injury caused by intrahepatic cAMP changes in different levels, in the study of mechanism and drug pharmacological effects should be considered