小鼠急性肺损伤后糖皮质激素受体的活性改变与热休克蛋白的关系

Association of glucocoid receptor binding activity and heat shock protein expressions after acute lung injury in mice

目的研究急性肺损伤(ALI)后机体内糖皮质激素受体(GR)的配体结合活性显著下降与其分子伴侣热休克蛋白(Hsps)改变的关系。方法以小鼠油酸急性肺损伤为模型,用Western blotting和受体的放射配体结合试验动态观察伤后GR、Hsp90、Hsp70和GR的结合容量和亲和力变化。结果伤后小鼠肺组织水肿、肺体指数和肺含水量显著升高;GR在伤后1h升高,然后显著下降,在12h达最低点;Hsp90和Hsp70在伤后的表达逐渐升高,在12h达最高点。配体结合试验显示在伤后GRBmax逐渐下降,Kd值升高,与Hsp90/GR的变化趋势一致。结论急性肺损伤后的GR配体结合活性的改变可能与Hsp90的变化有关。

Objective To study the associationbetween decreased ligand binding activity of glucocoid receptor （GR） and heat shock protein 90 （Hsp90）, the molecular chaperone of GR, after acute lung injury （ALI） in mice. Methods In mouse models of oleic acid-induced ALl, the levels of GR, Hsp90 and Hsp70 were dynamically observed using Western blotting, and the binding capacity and binding affinity of GR assessed with radioligand binding assay. Results After ALl, pulmonary edema was significantly aggravated in the mice with significantly increased lung body index and lung water ratio. GR increased within 1 h after the injury, but then decreased significantly to the lowest level at 12 h after the injury, and the levels of Hsp90 and Hsp70 was increased obviously and reached the highest at 12 h. Radioligand binding assay showed that the Bm^x decreased gradually and Kd value increased, and these changes were consistent with the changes of Hsp90/GR. Conclusion The ligand binding activity of GR is related to the changes of Hsp90 after ALI.