Objective: To observe the distribution and cell localization of TNF-alpha mRNA and its protein and study their role on pathogenesis of liver injury in rats.
Methods: An animal model in which rats were subjected to 20% TBSA III degree burns combined with intraperitoneal injection of lipopolysaccharide (LPS) was used for this experiment. The changes in the hepatic morphology, functions and TNF-alpha content in the serum and the expression, localization of liver TNF-alpha and TNF-alpha mRNA were determined with LM and EM, quantitative analysis, immunohistochemistry(IHC) and in situ hybridization (ISH).
Results: It was showed that there were sinusoid reaction, KCs activation and degeneration, necrosis of HCs, and platelets aggregation, fibrin deposition and PMNs attachment in sinusoid. The activity of ALT was obviously elevated and the content of ALB was slightly lowered. The contents of TNF-alpha in serum showed the peak values at 3 h. TNF-alpha was mainly localized in sinusoid endothelial cells(SECs), Kupffer cells (KCs) and TNF-alpha mRNA was mainly distributed in KCs, polymorphonuclear neutrophils (PMNs) and macrophages(MPs).
Conclusion: The results suggest that the expression and localization of TNF-alpha mRNA and its protein are in agreement with the pathological changes of liver injury. TNF-alpha is one of the key cytokines in pathogenesis of liver injury in rats after burns complicated by endotoxemia.