硫化氢缓释剂GYY4137对自发性高血压大鼠胸主动脉舒张功能的影响及机制研究  

Effects and mechanisms of slow-releasing hydrogen sulfide donor GYY4137 on vasodilation of thoracic aortic in spontaneously hypertensive rats

作　　者：马妍[1] 谢利平[1] 季勇[1] 

机构地区：[1]南京医科大学病理生理学系,江苏南京211166

出　　处：《南京医科大学学报（自然科学版）》2016年第5期549-553,共5页Journal of Nanjing Medical University(Natural Sciences)

基　　金：国家自然科学基金(31371156)

摘　　要：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.

关 键 词：硫化氢 自发性高血压大鼠 血管舒张 氧化应激 一氧化氮 

分 类 号：R972.4[医药卫生—药品]