淫羊藿苷通过抑制大鼠转化生长因子 -1/ 信号转导和转录激活因子通路减轻野百合碱诱导的肺动脉高压。
Icariin Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension via the Inhibition of TGF-1/Smads Pathway in Rats.
作者信息
Xiang Yijia, Cai Changhong, Wu Yonghui, Yang Lebing, Ye Shiyong, Zhao Huan, Zeng Chunlai
机构信息
Department of Cardiology, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang 323000, China.
出版信息
Evid Based Complement Alternat Med. 2020 Dec 1;2020:9238428. doi: 10.1155/2020/9238428. eCollection 2020.
BACKGROUND
Pulmonary artery remodeling is important in the development of pulmonary artery hypertension. The TGF-1/Smads signaling pathway is activated in pulmonary arterial hypertension (PAH) in rats. Icariin (ICA) suppresses the TGF-1/Smad2 pathway in myocardial fibrosis in rats. Therefore, we investigated the role of icariin in PAH by inhibiting the TGF-1/Smads pathway.
METHODS
Rats were randomly divided into control, monocrotaline (MCT), MCT + ICA-low, and MCT + ICA-high groups. MCT (60 mg/kg) was subcutaneously injected to induce PAH, and icariin (50 or 100 mg/kg.d) was orally administered for 2 weeks. At the end of the fourth week, right ventricular systolic pressure (RVSP) was obtained and the right ventricular hypertrophy index (RI) was determined as the ratio of the right ventricular weight to the left ventricular plus septal weight (RV/LV + S). Western blots were used to determine the expression of TGF-1, Smad2/3, P-Smad2/3, and matrix metalloproteinase-2 (MMP2) in lung tissues.
RESULTS
Compared to the control group, RVSP and RI were increased in the MCT group ( < 0.05). Additionally, TGF-1, Smad2/3, P-Smad2/3, and MMP2 expressions were obviously increased ( < 0.01). Compared to the MCT group, RVSP and RI were decreased in the MCT + ICA group ( < 0.05). TGF-1, Smad2/3, P-Smad2/3, and MMP2 expressions were also inhibited in the icariin treatment groups ( < 0.05). Icariin may suppress MCT-induced PAH via the inhibition of the TGF1-Smad2/3 pathway.
背景
肺动脉重塑在肺动脉高压的发展过程中起重要作用。转化生长因子-β1（TGF-β1）/Smads信号通路在大鼠肺动脉高压（PAH）中被激活。淫羊藿苷（ICA）可抑制大鼠心肌纤维化中的TGF-β1/Smad2信号通路。因此，我们通过抑制TGF-β1/Smads信号通路来研究淫羊藿苷在PAH中的作用。
方法
将大鼠随机分为对照组、野百合碱（MCT）组、MCT + ICA低剂量组和MCT + ICA高剂量组。皮下注射MCT（60 mg/kg）诱导PAH，并口服淫羊藿苷（50或100 mg/kg·d）2周。在第四周结束时，测量右心室收缩压（RVSP），并将右心室肥厚指数（RI）确定为右心室重量与左心室加室间隔重量之比（RV/LV + S）。采用蛋白质免疫印迹法检测肺组织中TGF-β1、Smad2/3、磷酸化Smad2/3（P-Smad2/3）和基质金属蛋白酶-2（MMP2）的表达。
结果
与对照组相比，MCT组的RVSP和RI升高（P < 0.05）。此外，TGF-β1、Smad2/3、P-Smad2/3和MMP2的表达明显增加（P < 0.01）。与MCT组相比，MCT + ICA组的RVSP和RI降低（P < 0.05）。淫羊藿苷治疗组中TGF-β1、Smad2/3、P-Smad2/3和MMP2的表达也受到抑制（P < 0.05）。淫羊藿苷可能通过抑制TGF-β1-Smad2/3信号通路来抑制MCT诱导的PAH。
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