脂多糖致大鼠急性肺损伤肺组织中糖皮质激素受体的表达及活性变化

目的探讨脂多糖致大鼠急性肺损伤24h内肺组织糖皮质激素受体(GR)表达及活性变化的特点。方法将70只Wistar大鼠随机分为脂多糖致伤组和地塞米松治疗组，采用RT-PCR和Western blot在mRNA水平和蛋白质水平测定致伤组肺组织GR，EMSA法测定肺组织GR活性。结果大鼠肺组织GR mRNA在致伤后表达下调，24h恢复至正常水平；肺组织GR蛋白质表达降低，伤后8h降至最低；肺组织GR活性在伤后1h降到最低，24h仍未恢复至正常水平。地塞米松治疗组在治疗后期不能有效维持GR活性。结论大鼠急性肺损伤肺组织GR蛋白表达降低，可能与mRNA表达降低及蛋白降解加速有关；GR活性被显著抑制，出现糖皮质激素抵抗。

Changes in glucocorticoid receptor expression and activity in lung tissue of acute lung injury induced by lipopolysaccharide in rats

Objective To investigate changes in glucocorticoid receptor (GR) expression and activity in lung tissue of acute lung injury induced by lipopolysaccharide (LPS) within 24h in rat. Methods A total of 70 Wistar rats were divided randomly into LPS treatment group and LPS+ Dexamethasone (Dex) treatment group. The GR mRNA and GR protein expressions in the lung tissue of LPS challenged rats were assessed by RT-PCR and Western blot at different time points. Electrophoretic mobility shift assays (EMSA) were used to determine the GR activity in the lung tissue. Results The expression level of GR mRNA was depressed, but it returned to normal level at 24h after LPS challenge. The expression level of GR was also lowered, reaching the lowest level at 8h. GR activity was decreased, reaching the lowest level at 1h, and remaining lower than that of normal control at 24h. Dex treatment showed no obvious effect on GR activity during the late period of treatment. Conclusion The GR protein expression decreases in lung tissue of acute lung injury in rats, and it maybe associated with the decreased expression of mRNA and accelerated degradation of GR protein. The activity of GR is inhibited sharply, resulting in glucocorticoid resistance.