一氧化氮和超氧阴离子在糖尿病小鼠创面愈合过程中的作用

Role of Nitric Oxide and superoxide playing on the trauma healing of the DM mice

目的了解在糖尿病小鼠模型的新鲜手术创面愈合过程中一氧化氮与超氧阴离子作用的分子机制。方法(1)建立链脲霉素(streptozotocin,STZ)诱导的Ⅰ型糖尿病小鼠创面模型;(2)检测糖尿病及正常对照组小鼠创伤前及创伤术后内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)蛋白表达水平及一氧化氮(nitric oxide,NO)水平;(3)采用选择性抑制剂,研究NAD(P)H氧化酶、黄嘌呤氧化酶和eNOS在糖尿病皮肤组织超氧阴离子(superoxide,O2-)产生机制中的地位。结果(1)链脲霉素可成功诱导小鼠形成稳定Ⅰ型糖尿病创面模型;(2)术后第5天正常对照组eNOS蛋白表达和NO水平显著升高(P<0.01),糖尿病组eNOS蛋白表达和NO水平则显著下降(P<0.05);(3)糖尿病小鼠皮肤组织O2-水平明显上升,NAD(P)H氧化酶抑制剂夹竹桃麻素(APO)和白屈菜赤碱(CHE)可明显抑制糖尿病皮肤组织O2-生成。结论糖尿病创面愈合与皮肤组织中eNOS、NO和O2-水平变化关系密切,而NAD(P)H氧化酶途径是调节糖尿病皮肤组织O2-生成的主要途径。

Objective To investigate the role of NO and Superoxide in the wound surface healing of DM model mice. Methods （1） Type ⅠDM mice induced by Streptozotocin was used as the animal model. （2）The levels of the Endothelial Nitric oxide Synthase （eNOS） expression and Nitric Oxide（NO） generation in the DM mice and the normal mice before and after the trauma-forming operation were examined. （3）The effect of using the selective inhibitions of NAD（P） H oxidase, xanthine oxidase and eNOS on the Superoxide generation was elucidated. Results （1）Type Ⅰ DM mice model induced by treptozotocin was established; （2）There was no difference of the eNOS level that was expressed in the skin between the DM mice and the normal mice, while the NO level was higher in the normal mice than DM mice before the trauma-forming operation（P〈0.05）. The eNOS protein and NO level were significantly increased in the normal mice on the fifth day after the trauma-forming operation than before （P〈0.01）, whereas decreased in the DM mice （P〈0. 05）. （3）The superoxide level in the DM mice＇s skin elevated after trauma. Using the APO and CHE could obviously decrease the superoxide forming. Conclusion The NO, eNOS and superoxide are important in DM mice trauma healing. High superoxide level is mainly coming from the NAD（P）H oxidase pathway.