ROCK1在地塞米松抑制中性粒细胞释放和单核细胞黏附中的作用  

Role of ROCK1 in dexamethasone-inhibited neutrophil release and monocyte adhesion in vitro

作　　者：刘冬[1] 熊仁平[1] 陈星云[1] 李平[1] 宁亚蕾[1] 彭艳[1] 赵艳[1] 杨楠[1] 周元国[1] 

机构地区：[1]第三军医大学大坪医院野战外科研究所分子生物学中心,创伤烧伤及复合伤国家重点实验室,重庆400042

出　　处：《第三军医大学学报》2012年第18期1814-1817,共4页Journal of Third Military Medical University

基　　金：国家自然科学基金(30470988);教育部创新团队基金(IRT0712)~~

摘　　要：目的探讨ROCK1在地塞米松(dexamethasone,Dex)抑制中性粒细胞释放和单核细胞黏附中的作用。方法检测地塞米松和法舒地尔(Fasudil,Fas)抑制佛波脂(PMA)诱导的中性粒细胞释放超氧化物阴离子(O2-)和髓过氧化物酶(myeloperoxidase,MPO)以及U937单核细胞黏附的程度,并检测ROCK1和RhoA的表达和活性改变。此外观察糖皮质激素受体拮抗剂——米非司酮(mifepristone,M)和蛋白质合成抑制剂——放线菌酮(cycloheximide,C)对地塞米松这些作用的影响。实验分组:对照组、PMA组、PMA+Dex组、PMA+Dex+M组、PMA+Dex+C组和PMA+Fas组。结果地塞米松可以显著抑制中性粒细胞释放O2-和MPO[(1.25±0.10)vs(1.95±0.10);(1.07±0.06)vs(1.75±0.08),P<0.05],而法舒地尔对其无明显抑制作用(P>0.05)。地塞米松和法舒地尔均可抑制U937细胞黏附[(0.09±0.01)vs(0.08±0.01)vs(0.28±0.06),P<0.05]。米非司酮和放线菌酮并不能影响地塞米松的这些作用(P>0.05)。结论地塞米松以非ROCK1依赖方式抑制中性粒细胞释放;以ROCK1依赖方式通过非基因组效应抑制U937单核细胞的黏附。Objective To determine the role of ROCK1 （Dex） on neutrophil release and monocyte adhesion. Methods in the inhibitory effect of dexamethasone The inhibitory effect of Dex and Fasudil （Fas） on the release superoxide anion （ O2- ） and myeloperoxidase （MPO） in neutrophil （PMN） after treat- ment of PMA, and the adhesion ability of U937 cells to human umbilical vein endothelial cells （HUVEC） after the stimulation as same as above mentioned was also determined. The expression and activity of ROCK1 and RhoA were also determined. Furthermore, the effect of glucocorticoid receptor antagonists （mifepristone, M） and protein synthesis inhibitors （cycloheximide, C） on dexamethasone were also evaluated. Cell samples were divided into control group, PMA group, PMA ＋ Dex group, PMA ＋ Dex ＋ M group, PMA ＋ Dex ＋ C group and PMA ＋ Fas group. Results Dex inhibited the release O2- and MPO of PMA-stimulated PMN （ 1.25 ±0.10 vs 1.95 ±0.10, 1.07±0.06 vs 1.75 ±0.08, P 〈0.05） but Fasudil had no this function （P 〉 0. 05 ）. Dexam- ethasone and Fasudil inhibited adhesion ability of U937 cells significantly （ 0.09 ± 0.01 and 0.08 ± 0.01 vs 0. 28± 0.06, P 〈 0. 05 ）. Mifepristone and cycloheximide did not interfere with the effect of Dex. Conclusion Dex inhibits the release of neutrophil via non-ROCK1 dependent pathway, and discourages U937 monocyte adhesion in ROCK1 dependent pathway via non-genomic effects.

关 键 词：地塞米松 非基因组效应 ROCK1 

分 类 号：R392.12[医药卫生—免疫学] R966[医药卫生—基础医学]