硫化氢对H_2O_2所致大鼠胸主动脉损伤的保护作用

Hydrogen sulfide has protective effect against H_2O_2-induced injury in isolated thoracic aorta of rats

目的:探讨硫化氢(hydrogen sulfide,H2S)对过氧化氢(hydrogen peroxide,H2O2)引起的大鼠离体胸主动脉损伤的保护作用和机制。方法:分离正常大鼠胸主动脉,制备主动脉环,利用300μmol/L H2O2建立大鼠胸主动脉环氧化应激损伤模型。25、50、100μmol/L的硫氢化钠(sodium hydrosulfide,NaHS)预处理后再用H2O2损伤大鼠胸主动脉环,应用血管功能检测张力仪比较各组舒张功能,并采用二氢乙啶(dihydroethidium,DHE)荧光染色法测定活性氧自由基(reactive oxygen species,ROS)的生成。Western blot法检测大鼠胸主动脉环中ERK1/2和磷酸化ERK1/2(p-ERK1/2)蛋白的表达。结果:300μmol/L的H2O2可引起大鼠胸主动脉环内皮依赖性舒张功能受损,50、100μmol/L的NaHS预处理后该损伤得到明显改善,使H2O2诱发的ROS亦显著减少。同时,H2O2可激活大鼠胸主动脉组织中的MAPK/ERK通路,使其磷酸化水平增加,而给予50、100μmol/L的NaHS预处理后可抑制该作用。结论:硫化氢对H2O2致大鼠胸主动脉氧化应激性损伤有保护作用,其机制可能与调节ERK信号通路有关。

Objective：To investigate the protective effect and mechanism of hydrogen sulfide （H2S） on hydrogen peroxide （H2O2）- induced injury in isolated thoracic aorta of rats. Methods：Thoracic aortic rings were isolated from normal Sprague-Dawley rats, subsequently exposed to 300 μmol/L H2O2 to establish an oxidative stress model. The thoracic aortic rings were pre-treated with 25 μmol/L,50 μmol/L or 100 μmol/L of NariS followed by incubation with 300 μmol/L H2O2. The endothelium-dependent vasorelaxant function of thoracic aortic rings was measured by a pressure transducer coupled to a Labchart V6 System. Production of ROS was evaluated using DHE fluorescent staining assay. The expressions of protein MAPK/ERK1/2 and p-ERK1/2 in thoracic aortic were determined by Western blot analysis. Results：H2O2 of 300 μmol/L can decrease vasorelaxant function in rats＇ thoracic aortic rings. Pre-treated with 50 μmol/L or 100 μmol/L of NariS can attenuate the damage and decrease the production of ROS caused by H2O2. H2O2 also activated MAPK/ERK pathway in the isolated rats＇ thoracic aorta,which could be inhibited by NariS of 50 μmol/L or 100 μmol/L. Conclusion：H2S may have protective effect against H2O2-induced injury through ERK signal pathway in isolated thoracic aorta of rats.