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目的:研究罗布麻叶提取物(extracts from leaves of Apocynum venetum,ELA)的抗高血压作用及其激活磷脂酰肌醇3激酶(PI3K)和(或)蛋白激酶B(Akt)信号转导通路促进一氧化氮释放的作用。方法:采用双肾双夹法建立Beagle犬高血压模型,随后按血压值将Beagle犬随机分为模型组(ig,生理盐水)、马来酸依那普利组(ig,1.66 mg.kg-1)、ELA低剂量组(ig 23mg.kg-1)、高剂量组(ig ELA 46 mg.kg-1)。受试动物在单次给予上述药物后,每隔1 h记录1次动物血压,连续8 h,观察ELA的降压作用;采用细胞培养法,观察ELA对内皮细胞(EAhy 926)一氧化氮(NO)产量和内皮型一氧化氮合酶(eNOS)活性的影响;采用Western blot法,观察ELA对eNOS,磷酸化内皮型一氧化氮合酶(p-eNOS)、磷酸化磷脂酰肌醇3激酶(p-PI3K)以及磷酸化蛋白激酶B(p-Akt)表达量的影响。结果:给药后,ELA高、低剂量组Beagle犬收缩压分别为(140.4±7.5),(136.2±6.8)mmHg;舒张压分别为(63.5±3.3),(72.2±4.4)mmHg;平均血压分别为(88.9±4.7),(93.3±5.2)mmHg,与给药前相比均显著降低(P<0.01);ELA可显著增加EA Hy926细胞NO的释放量(P<0.01),提高eNOS活性(P<0.01);Western blot结果表明,ELA可显著增加p-eNOS,p-PI3K以及p-Akt的表达量,与对照组相比,具有显著差异(P<0.01)。结论:ELA具有明显的降压作用。激活血管内皮细胞内PI3K/Akt信号转导途径,从而促进eNOS磷酸化,提高eNOS活性、增加NO可能是ELA降压作用的机制之一。
OBJECTIVE: To investigate the antihypertensive effects of extract from leaves of Apocynum venetum (ELA) and its role in the activation of phosphatidylinositol 3-kinase (PI3K) and / or protein kinase B (Akt) signaling pathways The role of nitric oxide release. Methods: Beagle dog model of hypertension was established by double-kidney double-clip method. Beagle dogs were randomly divided into model group (ig, normal saline) and enalapril maleate (ig, 1.66 mg.kg- 1), ELA low dose group (ig 23 mg.kg-1) and high dose group (ig ELA 46 mg.kg-1). Animals were given a single injection of the above drugs at 1 h intervals to record the blood pressure of animals for 8 h. The antihypertensive effect of ELA was observed. The effects of ELA on nitric oxide (NO) (NADH) in endothelial cells (EAhy 926) NO production and endothelial nitric oxide synthase (eNOS) activity. Western blot was used to observe the effect of ELA on eNOS, phosphorylation of endothelial nitric oxide synthase (p-eNOS), phosphorylated phosphatidylinositol 3 Kinase (p-PI3K) and phosphorylated protein kinase B (p-Akt) expression. RESULTS: After administration, the systolic blood pressure of Beagle dogs in high and low ELA groups were (140.4 ± 7.5) and (136.2 ± 6.8) mmHg, respectively; the diastolic blood pressure was (63.5 ± 3.3) and (72.2 ± 4.4) mmHg respectively; mean blood pressure (88.9 ± 4.7) and (93.3 ± 5.2) mmHg respectively, which were significantly lower than those before administration (P <0.01). ELA significantly increased NO release (P <0.01) and increased eNOS activity in EA Hy926 cells (P <0.01). The result of Western blot showed that ELA can significantly increase the expression of p-eNOS, p-PI3K and p-Akt compared with the control group (P <0.01). Conclusion: ELA has a significant antihypertensive effect. Activate the PI3K / Akt signal transduction pathway in vascular endothelial cells to promote eNOS phosphorylation, increase eNOS activity and increase NO may be one of the mechanisms of antihypertensive effect of ELA.