论文部分内容阅读
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 study the effect of GYY4137, a slow release hydrogen sulfide, on the diastolic function of thoracic aorta in spontaneously hypertensive rats (SHR) and to investigate its possible mechanism. Methods: Healthy 12-week-old SHRs were randomly divided into hypertensive control group (SHR group) and GYY4137 group, and male WKY rats of 12 weeks old were non-hypertensive control group (WKY group). GYY4137 group were intraperitoneally injected with GYY4137, SHR group and WKY group (GYY10 group), 25 mg / (kg · d) (GYY25 group) or 50 mg / (kg · d) The rats in the group were given the same amount of saline for 4 weeks, and the tail artery systolic blood pressure was measured every week during the administration. After 4 weeks of administration, the aortic diastolic function of the rats in each group was observed. The level of oxidative stress in the thoracic aorta was evaluated by DHE staining, malondialdehyde (MDA) and total antioxidant capacity (T-AOC) PI3K subunit p85α protein levels, phosphorylation of Akt and e NOS, and total protein levels. Results: After treatment with GYY4137, the endothelium-dependent vasodilation of thoracic aorta was significantly improved, the fluorescence intensity of DHE staining was decreased, the content of MDA was decreased, T-AOC was increased, the level of p85α protein and the phosphorylation of Akt and e NOS were increased. CONCLUSION: GYY4137 can improve the endothelium-dependent relaxation function of the thoracic aorta in SHR. The mechanism may be related to the anti-oxidative stress and the activation of the PI3K / Akt / e NOS signaling pathway.