Experimental study on early liver injury and expressions of TNF-alpha mRNA in burn rats with endotoxemia / 中华创伤杂志(英文版)

ABSTRACT

OBJECTIVE: To observe tissue distribution and cell localization of TNF-alpha mRNA and its protein and study their role in the pathogenesis of liver injury in burn rats. METHODS: An animal model of rats subjected to 20% TBSA III degree burns combined with intraperitoneal injection of lipopolysaccharide (LPS) was used for this experiment. The changes of hepatic morphology and functions and serum TNF-alpha content and expression and localization of liver TNF-alpha and TNF-alpha mRNA were determined with light microscope (LM) and electron microscope (EM), quantitative analysis, immunohistochemistry (IHC) and in situ hybridization (ISH). RESULTS: It showed that there were sinusoid reaction, KCs activation and degeneration, necrosis of HCs, and platelets aggregation, fibrins deposition and PMNs attachment in sinusoid. The activity of ALT was obviously elevated and ALB content was slightly decreased. The serum content of TNF-alpha showed peak at 3 hours. TNF-alpha was mainly localized in sinusoid endothelial cells (SECs) and Kupffer cells (KCs), and TNF-alpha mRNA was mainly distributed in KCs, polymorphonuclears neutrophils (PMNs) and macrophages (MPs). CONCLUSIONS: It suggests that TNF-alpha mRNA and its protein expression and localization are coincident with the pathological changes of liver injury. TNF-alpha is one of the key cytokines in the pathogenesis of liver injury in burn rats with endotoxemia.