一氧化氮供体型氢化可的松衍生物Ⅱ_5的抗炎及血管舒张活性研究  

Anti-inflammatory and vasorelaxant effects of NO-donating hydrocortisone derivatives Ⅱ_(5)

作　　者：丁大永[1] 季晖[1] 房雷[2] 张奕华[2] 李永齐[1] 

机构地区：[1]中国药科大学药理学教研室 [2]中国药科大学新药研究中心,南京210009

出　　处：《中国药科大学学报》2006年第4期353-357,共5页Journal of China Pharmaceutical University

摘　　要：目的 研究一氧化氮（NO）供体型氢化可的松衍生物Ⅱ5的抗炎活性及对大鼠主动脉环的松弛作用。方法：采用小鼠耳二甲苯致炎模型对硝酸酯类和呋咱氮氧化物类一氧化氮供体型氢化可的松衍生物进行抗炎活性筛选，用角叉菜胶致大鼠足跖肿胀模型、棉球肉芽肿模型进一步研究活性化合物Ⅱ5的抗炎作用，Greiss法检测化合物Ⅱ5体外NO的释放情况，大鼠胸主动脉环收缩性实验检测化合物Ⅱ5对血管紧张性的影响。结果：化合物Ⅱ5对二甲苯诱导的小鼠耳肿胀和角叉菜胶诱导的大鼠足跖肿胀的急性炎症，以及对棉球诱导的大鼠慢性肉芽组织增生都有明显的抑制作用，并具有一定的剂量相关性。体外释放NO约在3h时接近最大释放值（0．905μg/mL），在其后的3h内较稳定（维持在0．905～0．957μg/mL）。对大鼠胸主动脉具有显著的舒张作用，其IC50为（139±57）nmol／L。结论：NO供体型氢化可的松衍生物Ⅱ5具有较强的抗炎活性，在体外能平稳释放低水平的NO，对大鼠胸主动脉具有明显的舒张作用。Aim： To investigate the anti-inflammatory and vasorelaxant effects of NO-donating hydrocortisone derivatives in the rat model. Methods： Screening of anti-inflammatory effects of NO-donating （Nitrate esters and Furoxan） hydrocortisone derivatives were observed in the rat of xylene-induced ear edem, and anti-inflammatory effects of compound Ⅱ5 were further studied in the rat of carrageenin-induced hind paw edema and the cotton pellet-induced granuloma. NO release was determined in vitro by Griess method. In addition, vasorelaxationt effects of compound Ⅱ5 were assessed by observation of the contractions of thoracic aorta of rots. Results： Compound Ⅱ5 significantly inhibited xylene-induced ear edema and carrageenin-induced hind paw edema in the acute inflammatory rats, and also exhibited pronounced inhibitory activity on the formation of granuloma in the chronic inflammatory rat model of cotton pellet- induced granuloma. The effects were found to be dose-dependent. In vitro determination of NO releasing showed that the level of NO reached the maxima at 3 h and varied between 0.905 and 0.957μg/mL in the following 3 hours Moreover, Compound Ⅱ5 caused marked relaxation on the NA-precontracted aortic rings with IC50 of 139 ± 57 nmol/L. Conclusion： NO-donating hydrocortisone derivative Ⅱ5, has potet anti-inflammatory effect, while it could relax aortic rings of rats, perhaps due to NO releasing.

关 键 词：一氧化氮供体型氢化可的松 抗炎作用 主动脉环 血管舒张作用 

分 类 号：R96[医药卫生—药理学]