| It is well known that different individuals may have different glucocorticoid (Gc) efficiency caused by genetic heterogeneity. Recent studies have demonstrated that 6.6% of the normal population was relatively hypersensitive to glucocorticoids, while 2.3% was relatively resistant. Although a few clinical cases whose kindred are resistant to glucocorticoid have been confirmed that they have glucocorticoid receptor (GR) gene heterogeneity, there still have many cases without being detected GR gene heterogeneity mentioned before. Thus, some researchers conceived that any change in the Gc-GR signal transduction pathway might cause different Gc-GR efficiency. The difference of individual Gc-GR efficiency would definitely influence the progress and therapy of the correlated diseases. Heat shock protein 90s (HSP90s), an indispensable chaperone protein, play an important role in modulating the Gc-GR pathway focus on GR, such as GR maturing, conformation maintenance, ligand binding, nucleic translocation and GR intranuclear circulation.Acute pancreatitis (AP) is a clinical entity that is believed to have intracellular activation of digestive enzymes and autodigestion of the pancreas as its central pathophysiologic cause. This noninfectious destruction of pancreatic parenchyma quickly induces an inflammatory reaction at the site of injury,even activates the cascade of inflammatory mediators. The amplification of inflammatory cytokines could cause systemic inflammatory response syndrome (SIRS), or even multiple organs dysfunction syndrome (MODS). As an important nonspecific inhibitor of inflammatory mediators, Gc can inhibit the expression of inflammatory cytokines, ameliorate microcirculation and relieve oxygen-derived free radidicals. Anti-inflammatory effect of Gc-GR is believed to play an important role during the occurrence and process of AP up to now.Several discrepancies of HSP84, an isoform of HSP90, between the two strains of C57BL/6 and BALB/c mice had been discovered by our laboratory. Further study had confirmed that those discrepancies could affect Gc-GR efficiency via modulating nucleictranslocation. Base on the role of Gc-GR effect in AP, we considered whether the AP model of the two strains mice had different prognosis, whether its mechanism correlated to the discrepancies of HSP90.The death rate and the expression of interleukin-1β were observed in the two strains mice with experimental pancreastitis induced by injecting L-arginine (Arg) to the abdominal cavity and/or treated with different dosage of Gc. The possible mechanisms of the different anti-inflammatory efficiency of the Gc-GR were explored by examining the signal pathway of Gc-GR.The main conclusions of the study are as below:1. The AP model induced by injecting L-arginine (Arg) to the abdominal cavity of mice has some advantages as below, easy producing, low prices, good reproducibility, little injury, avoiding laparotomy and decreasing infections caused by ectogenesis bacteria.2. The results showed that C57BL/6 AP mice had a lower death rate and interleukin-1β level than BALB/c mice, but no difference of the concentration of amylase between two strains mice was observed. It suggested the significant difference in death rate and pathological damage were not relative to the concentration of amylase, but may relate to the difference of inflammatory reaction in two strains mice. 3. Results of AP mice treated with different dosage Gc showed that low dosage (0.4mg/kg BW) decreased the expression of interleukin-1β of C57BL/6 mice, but with minor effects on that of BALB/c; High dosage (4mg/kg BW) Gc decreased the expression of interleukin-1β in both strains, and the inhibitory action in C57BL/6 was more effective than BALB/c in 24h and 36h. These results indicated that the Gc-GR anti-inflammatory effects might be different between two strains mice, and high dosage Gc may make up this difference.4. Results of EMSA showed that GRE binding activity of the pulmonary nuclear extract of C57BL/6 mice in all phases were signi...
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