Effects Of Alterations Of Coagulation Activity On Inflammation And Its Mechanism In Old Rats

Background. Coagulation abnormalities and fibrin deposition has beenobserved in most types of human inflammations, and related with inflammatoryinjure. Basic studies proved that coagulation system involved in inflammatoryregulations. Epidemiological survey data indicated that there was pronouncedprocoagulant state in old people. In the same time, the susceptibility of elderlypatients to infection was enhanced. We presume that coagulation over-activationaggravate inflammation. However, the mechanisms for aging accelerationcoagulation activity and coagulation effect inflammation in old people remainunclear. Objective. To test our hypothesis, we explore the mechanism for agingcontributing to pronounced procoagulant activities. Furthermore, coagulationactivity was controlled by pharmaceutical methods, to determine the mechanismof coagulation over-activation aggravate inflammation of old rats in vivo. Finally,to explore the molecule mechanism of coagulation effect inflammation in vitro.Methods. Both young and aged rats with acute inflammation induced bylipopolysaccharide (LPS) were treated with tranexamic acid (TA) and TA plasurokinase (UK) or heparin (HP). Comparisons were made between six treatmentgroups within the same age groups, as well as between two age groups with asame treatment. Fibrin deposition were detected by immunofluorescence stainingand analyzed by laser scanning confocal microscopy. The expressions of proteinand gene were determined by immunochemohistory staining, Western blot andNorthern blot. Results. (1) There were no protein and gene expression ofplasminogen activator inhibitor-1 (PAI-1) in normal control groups, but that ofthrombomodulin (TM) were abundant. In LPS groups, PAI-1 protein and geneexpressions in lung and renal were significantly increased, and PAI-1expressions of aged rats were higher than that of young (P<0.05);TMexpressions of LPS groups were hardly detected. (2) Compared with LPS group, infiltrating inflammatory cells and expressions of monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule 1 (ICAM-1) were markedly upregulated in LPS plus TA group (.PO.05), being accompanied with increased fibrin deposits and thrombin receptor (TR) expression (PO.05). Reduction of fibrin deposition and TR expression in LPS+TA+HP groups was associated with downregulation of the above indices (PO.05). It was fibrin deposition but not TR expression that reduced in LPS+TA+UK groups, however, above indices still downregulated (PO.05). (3) Interestingly, there were significant differences in fibrin deposition and TR expression between young and aged groups after a same treatment (PO.05). And there were also significant differences in increased infiltrating inflammatory cells and expressions of MCP-1 and ICAM-1 between young and aged rats (PO.05). (4) In vitro, fibrin and TR pathway all can induce ICAM-1 expression on endothelium, but the effect of fibrin was significiatly stronger than TR pathway (PO.01). Fibrin significiatly increased the monocytes adhension to endothelium than TR pathway. Conclusion (1) These in vivo data demonstrated that aging might contribute to pronounced procoagulant state by upregulating PAI-1 and downregulating TM expression. (2) Fibrin deposition and TR pathway contributed to inflammatory responses by inducing adhesion molecule and chemokines expression, which could be exacerbated by aging. (3) These in vitro data demonstrated that fibrin play important role in the modulation of coagulation on inflammation...