葛根素对高血压大鼠内皮功能障碍的影响

Influence of Puerarin on Endothelial Dysfunction in Hypertensive Rats

关键词:  血管紧张素Ⅱ  葛根素  内皮功能  高血压  氧化应激

Key words:  angiotensin Ⅱ  puerarin  endothelial function  hypertension  oxidative stress

摘要:

目的 研究葛根素对血管紧张素(angiotensin，Ang)Ⅱ诱导的高血压大鼠的影响，并探讨其改善内皮功能的机制。方法 SD大鼠随机分为对照组、Ang Ⅱ组和葛根素组。Ang Ⅱ组连续5 d泵入Ang Ⅱ(0.7 mg·kg^-1·d^-1)，葛根素组在泵入Ang Ⅱ前10 d采用葛根素注射液腹腔注射(100 mg·kg^-1·d^-1)进行干预。采用尾动脉法测量收缩压，用血管张力测量灌流系统测量内皮依赖性舒张功能(endothelium-dependent relaxation，EDR)。Western blot测量血管内相关蛋白的表达。结果 葛根素能明显降低Ang Ⅱ诱导的大鼠高血压水平(P<0.05)，减轻Ang Ⅱ引起的动脉内膜增厚和心肌细胞的肥大。和对照组相比，Ang Ⅱ组能削弱动脉血管的EDR，同时降低p-eNOs(Ser 1177)的表达，增强gp91 phox(85%)，p22 phox(113%)的表达，而葛根素能改善EDR，并逆转Ang Ⅱ引起的蛋白量的变化。结论 在Ang Ⅱ诱导的高血压大鼠中，葛根素能降低血压，保护内皮功能及靶器官免受损伤。葛根素具有心血管保护作用，机制可能和自身抗氧化及上调p-eNOs的作用有关。

Abstract:

OBJECTIVE To investigate the effect of puerarin on endothelial function in angiotenin (Ang) Ⅱ-induced hypertensive rats as well as the underlying mechanism of improving endothelial function. METHODS SD rats were randomly divided into control, Ang Ⅱ and puerarin groups. The rats of Ang Ⅱ groups were infused with Ang Ⅱ (0.7 mg·kg^-1·d^-1 implanted by mini-pump) for 5 d while the rats of puerarin group were treated with puerarin (100 mg·kg^-1·d^-1) for 10 d followed by Ang Ⅱ and puerarin for 5 d. The systolic blood pressure (SBP) was measured by tail-cuff method. Endothelium-dependent relaxation (EDR) to acetylcholine was determined using organ chamber bath. Expression of the protein in the aortic tissue was determined by Western blot analysis. RESULTS Puerarin significantly reduced SBP (P<0.05), aortic and LV hypertrophy in Ang Ⅱ-infused rats. Puerarin also reduced aortic medial thickness and myocardial cell surface area in Ang Ⅱ-infused rats. Compared with the rats in control group, Ang Ⅱ infused rats exhibited an impaired EDR with reduction in the protein expression of phosphor-eNOS at ser 1177 and increase the expression of gp91phox (85%), p22phox (113%). Puerarin improved EDR and reversed the changes of Ang Ⅱ-induced protein expression of above molecules. CONCLUSION Puerarin reduced blood pressure, improved endothelial function and end organ damage in Ang Ⅱ-induced hypertensive rats, the anti-oxidant and upregulation of phosphor-eNOS of puerarin may in part contribute to its cardiovascular protective effects.