Regularity in organ injuries and roles of TNF-α in multiple organ dysfunction syndrome induced by oleic acid and lipopolysaccharide in elderly rats

Objective To investigate the regularity in organ injuries and the roles of tumor necrosis factor alpha (TNF-α) in multiple organ dysfunction syndrome in the elderly rats (MODSE). Methods Models of MODSE and multiple organ dysfunction syndromes in the young (MODSY) were established respectively by injection of oleic acid (OA) at the dose of 0.25 ml/kg and lipopolysaccharide (LPS) at the dose of 3.5 mg/kg) into SD rats (4 h interval). A total of 40 3-month-old and 40 20-month-old SD rats were randomly divided into four groups respectively: saline control group (n=10) and three model groups (n=30) including 2-, 6-, and 24-h groups. Incidences of MODS were diagnosed by their criteria. The changes of the partial pressure of arterial oxygen (PaO 2) level were observed. Serum levels of alanine aminotransferase (ALT), total bilirubin (TB), blood urea nitrogen (BUN), creatinine (Cr), and creatine phosphokinase (CPK) were measured by the automatic biochemistry analyzer. The TNF-α contents in plasma and in the lung, heart, liver, and kidney were determined with enzyme linked immunosorbent assay (ELISA). Results Injection of OA and LPS into the young and the elderly rats led to multiple organs dysfunctions. PaO 2 of Young Group and Elderly Group decreased to minimum at 2 h [(67.5±8.66) and (59.3±7.41) mmHg, respectively, P0.01]. While the biochemical indexes of the heart, liver, and kidney organ injuries increased to maximum at 6 h (P0.05, P0.01). Furthermore, the organs in Elderly Group were damaged more seriously than those in Young Group at the same time points (P0.05, P0.01). TNF-α concentrations in plasma and organs increased significantly (especially in the lungs) after LPS injection and peaked at 2 h after damage (P0.05, P0.01). TNF-α levels were higher in Elderly Group than those in Young Group at the same time points (P0.05, P0.01). Conclusion OA and LPS injection can lead to more serious multiple organ injuries in elder rats than those in young rats. The lung is injured firstly and most seriously. Early and quickly increase of TNF-α concentration in the lungs may be an important pathophysiological mechanism of MODSE.