刺五加苷E对野百合碱诱导肺动脉高压模型大鼠的治疗作用  

Therapeutic Effects of Eleutheroside E on Monocrotaline Induced Pulmonary Arterial Hypertension in Rats

作　　者：田京辉 郭姗姗 陈静静 徐炳欣 赵亮 TIAN Jinghui;GUO Shanshan;CHEN Jingjing;XU Bingxin;ZHAO Liang(Department of Pharmacy,Xuchang Central Hospital Affiliated to Henan University of Science and Technology,Xuchang 461000,China;Xuchang Key Laboratory of Molecular Medicine,Xuchang 461000,China;Department of Biochemical Pharmacy,School of Pharmacy,the Second Military Medical University,Shanghai 200433,China)

机构地区：[1]河南科技大学附属许昌市中心医院药学部,许昌461000 [2]许昌市分子医学重点实验室,许昌461000 [3]第二军医大学药学院生化药学教研室,上海200433

出　　处：《医药导报》2022年第2期216-220,共5页Herald of Medicine

摘　　要：目的观察刺五加苷E对野百合碱(MCT)诱导肺动脉高压(PAH)大鼠的治疗作用,并探讨其可能作用机制。方法将48只雄性SD大鼠随机分为4组,每组12只,采用颈背部皮下注射MCT法诱导建立PAH模型,并于MCT诱导后1周开始进行刺五加苷E干预(10 mg·kg^(-1),腹腔注射,1天1次);连续给药2周后,采用右心导管检测大鼠血流动力学;Fulton’s指数计算大鼠右心肥厚程度;苏木精-伊红(HE)染色和免疫荧光实验评估大鼠肺血管病理性重构与肌化水平;Western blotting实验评估大鼠肺组织中PI3K、Akt的磷酸化水平。结果腹腔注射刺五加苷E后,PAH大鼠血流动力学得到明显改善,其右心室收缩压显著降低[(33.18±4.85)和(44.95±3.59)mmHg,P<0.01],平均肺动脉压亦显著降低[(31.77±5.41)和(42.20±3.18)mmHg,P<0.01];刺五加苷E干预显著改善PAH大鼠右心肥厚指数[(0.29±0.03)和(0.41±0.07),P<0.01];组织病理学结果显示刺五加苷E有效抑制PAH大鼠肺血管中膜厚度[(34.88±3.24)%和(47.67±2.88)%,P<0.01]和血管肌化水平[(38.8±3.42)%和(53.80±6.76)%,P<0.05];Western blotting结果提示刺五加苷E显著抑制PAH大鼠肺组织中PI3K和Akt蛋白的磷酸化水平。结论刺五加苷E通过调节PI3K/Akt途径对PAH起到治疗作用。Objective To observe the therapeutic effect of eleutheroside E on monocrotaline(MCT)induced pulmonary arterial hypertension(PAH)rats and to explore its possible mechanism.Methods Forty-eight male Sprague-Dawley rats were randomly divided into 4 groups.For the intervention group,rats received intraperitoneal injection of eleutheroside E(10 mg·kg^(-1),once daily)at day 7 after one-dose subcutaneous injection of MCT.After intervention for 2 weeks,the right heart catheter was adopted to evaluate the hemodynamics.Fulton’s index was used to calculate the right heart hypertrophy.HE staining and immunofluorescence staining were used to evaluate the pulmonary vascular remodeling,and Western blotting was used to assess the phosphorylation of PI3 K and Akt in lung tissue of SD rats.Results After intraperitoneal administration of eleutheroside E,the hemodynamics of PAH rats were significantly improved,with a mark decrease in right ventricular systolic pressure(33.18±4.85 v.s.44.95±3.59 mmHg,P<0.01)and mean pulmonary artery pressure(31.77±5.41 v.s.42.20±3.18 mmHg,P<0.01)compared to MCT group.Eleutheroside E also significantly improved right heart hypertrophy index in PAH rats(0.29±0.03 v.s.0.41±0.07,P<0.01).Pathological staining showed that eleutheroside E effectively inhibited pulmonary artery media thickness(34.88±3.24)%v.s.(47.67±2.88)%(P<0.01),and muscuralization(38.8±3.42)v.s.(53.80±6.76)%(P<0.05)in PAH rats.Western blotting indicated that eleutheroside E significantly inhibited the phosphorylation of PI3 K and Akt in the lungs of PAH rats.Conclusion Eleutheroside E exerts a therapeutic effect on PAH by regulating the PI3 K/Akt pathway.

关 键 词：刺五加苷E 肺动脉高压 血流动力学 血管重构 

分 类 号：R965[医药卫生—药理学] R563.9[医药卫生—药学]