目的 :研究硫化氢缓释剂GYY4137对自发性高血压大鼠(spontaneously hypertensive rats,SHR)胸主动脉舒张功能的影响,并初步探讨其机制。方法:健康12周龄雄性SHR随机分为高血压对照组(SHR组)和GYY4137组,雄性12周龄WKY大鼠为非高血压对照组(WKY组)。GYY4137组分别腹腔注射10 mg/(kg·d)(GYY10组)、25 mg/(kg·d)(GYY25组)或50 mg/(kg·d)(GYY50组)的GYY4137,SHR组和WKY组给予等量生理盐水,连续4周,给药期间每周测定尾动脉收缩压。给药4周后观察各组大鼠胸主动脉舒张功能,通过DHE染色、丙二醛(MDA)和总抗氧化能力(T-AOC)测定评价胸主动脉氧化应激水平,Western blot方法检测PI3K亚单位p85α蛋白水平,Akt及e NOS的磷酸化及总蛋白水平。结果:GYY4137治疗后,胸主动脉内皮依赖性舒张功能明显改善,DHE染色荧光强度减弱,MDA含量降低,而T-AOC有所上升,p85α蛋白水平以及Akt、e NOS磷酸化水平增加。结论:GYY4137可以改善SHR胸主动脉内皮依赖性舒张功能,其机制可能与抗氧化应激以及激活PI3K/Akt/e NOS信号通路有关。
Objective:To observe the effects and study the mechanisms of slow-releasing hydrogen sulfide donor GYY4137 on the vasodilation of thoracic aortic in spontaneously hypertensive rats(SHRs). Methods:Male SHRs at 12 weeks of age were randomly divided into 4 groups treated with different dosages of GYY4137:0(SHR group),10(GYY10 group),25(GYY25 group)or 50(GYY50group)mg / kg / day. GYY4137 was given by intraperitoneal injection once daily for 4 weeks. Age-matched normotensive Wistar-Kyoto(WKY)rats served as controls(WKY group). SHR and WKY control groups received the same volume of physiological saline. During treatment,systolic blood pressure(SBP)was measured by the tail-cuff method. After 4 weeks,vasodilation of thoracic aortic was measured. The degree of oxidative stress was evaluated by DHE staining,malondialdehyde(MDA)and total antioxidant capacity(TAOC). The expression of p85α,Akt,p-Akt(Ser473),e NOS and p-e NOS(Ser1177)was detected by western blot. Results:After treatment,GYY4137 improved endothelium-dependent vasodilation of thoracic aortic in SHRs,lessened the superoxide generation,decrease MDA level,enhanced T-AOC,and increased the protein level of p85α and the phosphorylation of Akt and e NOS. Conclusion:GYY4137 improved endothelium-dependent vasodilation of SHRs,which may be associated with the suppression of oxidative stress and activation of PI3 K / AKT / e NOS signal pathway.