淫羊藿苷对去势自发性高血压大鼠平均动脉压、心率、血清NO及ET-1的影响

Effects of Icariin on Mean Arterial Pressure,Heart Rate,Serum NO,and ET-1 in Ovariectomized Female Spontaneously Hypertensive Rat

目的观察淫羊藿苷对去势雌性自发性高血压大鼠平均动脉压(MAP)、心率、血清一氧化氮(NO)及内皮素-1(ET-1)水平的影响,并探讨其作用机制。方法9周龄清洁级雌性自发性高血压大鼠(SHR)36只及9周龄清洁级具有相同遗传背景的正常血压雌性京都Wistar大鼠6只,给予普通饲料适应性喂养1周,继而行无菌卵巢切除术。Wistar去势雌性大鼠为空白组,SHR去势雌性大鼠随机分为模型组、雌激素组、淫羊藿苷低剂量组、淫羊藿苷中剂量组、淫羊藿苷高剂量组、淫羊藿苷中剂量+氟维司群组,每组6只,分别给予相应药物8周后检测各组大鼠MAP及心率、NO及ET-1水平、磷酸化蛋白激酶B(p-Akt)蛋白及蛋白激酶B(Akt)总蛋白表达。结果与空白组比较,模型组MAP明显升高(P<0.01);与模型组比较,雌激素组、淫羊藿苷低剂量组、淫羊藿苷中剂量组及淫羊藿苷高剂量组MAP明显降低(P<0.01);与淫羊藿苷中剂量组比较,淫羊藿苷中剂量+氟维司群组MAP明显升高(P<0.01)。与模型组比较,淫羊藿苷低剂量组、淫羊藿苷中剂量组及淫羊藿苷高剂量组心率明显降低(P<0.01);与淫羊藿苷中剂量组比较,淫羊藿苷中剂量+氟维司群组心率明显升高(P<0.01)。与空白组比较,模型组血清NO水平明显下降(P<0.01)而血清ET-1水平明显升高(P<0.01);与模型组比较,雌激素组、淫羊藿苷低剂量组、淫羊藿苷中剂量组及淫羊藿苷高剂量组血清NO水平明显升高(P<0.05)而血清ET-1水平明显降低(P<0.05);与雌激素组比较,淫羊藿苷低剂量组、淫羊藿苷中剂量组血清NO水平明显升高(P<0.01);与淫羊藿苷中剂量组比较,淫羊藿苷中剂量+氟维司群组血清NO水平明显下降(P<0.05)而血清ET-1水平明显升高(P<0.05)。与空白组比较,模型组主动脉p-Akt/Akt相对表达量水平明显升高(P<0.01);与模型组比较,雌激素组、淫羊藿苷低剂量组、淫羊藿苷中剂量组及淫羊藿苷高剂量组主动脉p-Akt/Akt相对表达量水平明显降低(P<0.05);与淫羊藿苷中剂量组比较,淫羊藿苷中剂量+氟维司群组主动脉p-Akt/Akt相对表达量水平明显升高(P<0.05)。结论淫羊藿苷作为一类植物类雌激素,降血压作用与调节NO及ET-1的分泌量及功能有关。

Objective To observe the effect of Icariin on mean arterial pressure(MAP),heart rate,plasma nitric oxide(NO),and serum endothelin-1(ET-1)levels in ovariectomized female spontaneously hypertensive rat(SHR),and explore its mechanism.Methods Thirty-six nine-week-old clean grade female SHR rats and six nine-week-old clean grade female Wistar Kyoto rats with normal blood pressure were fed with normal diet for one week,followed by aseptic ovariectomy.Ovariectomized female Wistar Kyoto rats as blank group,ovariectomized female SHR rats were randomly divided into model group,estrogen group(SHR-E2),Icariin low-dose group(SHR-LI),Icariin middle-dose group(SHR-MI),Icariin high-dose group(SHR-HI),Icariin middle-dose+estrogen receptor antagonist group(SHR-MI+ICI),with 6 rats in each group.MAP and heart rate,NO and ET-1 levels,phosphorylated protein kinase B(P-Akt),and total protein kinase B(Akt)expression of rats in each group were detected at 8 weeks after corresponding drugs treatment.Results Compared with blank group,the MAP of model group was increased significantly(P<0.01).Compared with model group,the MAP of SHR-E2,SHR-LI,SHR-MI,and SHR-HI was reduced significantly(P<0.01).Compared with SHR-MI,the MAP of SHR-MI+ICI was increased significantly(P<0.01).Compared with model group,the heart rate of SHR-LI,SHR-MI,and SHR-HI was reduced significantly(P<0.01).Compared with SHR-MI,the heart rate of SHR-MI+ICI was increased significantly(P<0.01).Compared with blank group,the serum NO level of model group was reduced significantly(P<0.01)and serum ET-1 level was increased significantly(P<0.01).Compared with model group,the serum NO level of SHR-E2,SHR-LI,SHR-MI,and SHR-HI was increased significantly(P<0.05)and serum ET-1 level was reduced significantly(P<0.05).Compared with SHR-E2,the serum NO level of SHR-LI,SHR-MI was increased significantly(P<0.01).Compared with SHR-MI,the serum NO level of SHR-MI+ICI was reduced significantly(P<0.05),and serum ET-1 level was increased significantly(P<0.05).Compared with blank group,the relative expressions of p-Akt:Akt of model group in aorta was increased significantly(P<0.01).Compared with model group,the relative expressions of p-Akt:Akt of SHR-E2,SHR-LI,SHR-MI,and SHR-HI was reduced significantly(P<0.05).Compared with SHR-MI,the relative expressions of p-Akt:Akt of SHR-MI+ICI was increased significantly(P<0.05).Conclusion Icariin,as a phytoestrogen,can reduce blood pressure by regulating the secretion and function of NO and ET-1.