Li Lei, Dong Pengda, Hou Congjia, Cao Fangyuan, Sun Shouli, He Fa, Song Yanping, Li Sen, Bai Yuhua, Zhu Daling
College of Pharmacy, Harbin Medical University, Daqing 163319, China.
The fifth affiliated Hospital of Harbin Medical University, Daqing 163316, China.
J Ethnopharmacol. 2016 Jun 20;186:224-233. doi: 10.1016/j.jep.2016.04.004. Epub 2016 Apr 5.
Carthamus tinctorius L. is a traditional herbal medicine native to China with properties of promoting blood circulation and removing blood stasis, which is used for the treatment of cerebrovascular and cardiovascular diseases. Hydroxysafflor yellow A (HSYA) is the main constituent isolated from the flower of Carthamus tinctorius L. which is used as a marker substance in the quality control of Carthamus tinctorius L. in Chinese Pharmacopeia.
This study is to investigate the hypertension attenuating effect of HSYA on hypoxia-induced pulmonary artery hypertension model rats, and the possible mechanism.
The animal models were made by treating adult male Wistar rats (of the same age with the same weight of 200±25g) under hypoxia 24h per day for 9 days with or without administration of HSYA. The pulmonary arterial pressure of rats was measured after anesthetization; The right ventricular hypotrophy was evaluated by the right ventricular hypotrophy index (RVHI=[RV/(LV+S)]) as well as histomorphology assay with Hematoxylin and Eosin (HE) staining; The reducing of pulmonary artery remodelling was evaluated by histomorphology assay with HE staining; The proliferation of pulmonary artery smooth muscle cells (PASMCs) was evaluated by immunohistochemistry assays (PCNA and Ki67) and MTT assay. Cell cycle analysis and Weston-blot analysis were also performed in the study.
HSYA reduced the mean right ventricular systolic pressure (RVSP) of rats with hypoxic pulmonary arterial hypertension (HPH) in a manner of concentration dependency. It significantly inhibited the PASMCs proliferation and attenuated the remodelling of the pulmonary artery and right ventricular hypertrophy.
These findings suggested that HSYA protected against hypoxic induced pulmonary hypertension by reversing the remodelling of the pulmonary artery through inhibiting the proliferation and hypertrophy of PASMCs. This is in accordance with our previous finding that HSYA protects against the pulmonary artery vascular constriction. All these results suggest that HSYA may be a promising candidate for HPH treatment.
红花是一种原产于中国的传统草药，具有促进血液循环和祛瘀的特性，用于治疗脑血管和心血管疾病。羟基红花黄色素A（HSYA）是从红花中分离出的主要成分，在中国药典中用作红花质量控制的指标性成分。
本研究旨在探讨HSYA对低氧诱导的肺动脉高压模型大鼠的降压作用及其可能机制。
将成年雄性Wistar大鼠（年龄相同，体重200±25g）每天低氧处理24小时，持续9天，分别给予或不给予HSYA，制备动物模型。麻醉后测量大鼠肺动脉压；通过右心室肥厚指数（RVHI = [RV / (LV + S)]）以及苏木精-伊红（HE）染色的组织形态学分析评估右心室肥厚；通过HE染色的组织形态学分析评估肺动脉重塑的减轻情况；通过免疫组织化学分析（PCNA和Ki67）和MTT分析评估肺动脉平滑肌细胞（PASMCs）的增殖。本研究还进行了细胞周期分析和蛋白质免疫印迹分析。
HSYA以浓度依赖性方式降低了低氧性肺动脉高压（HPH）大鼠的平均右心室收缩压（RVSP）。它显著抑制了PASMCs的增殖，减轻了肺动脉重塑和右心室肥厚。
这些发现表明，HSYA通过抑制PASMCs的增殖和肥厚，逆转肺动脉重塑，从而预防低氧诱导的肺动脉高压。这与我们之前发现的HSYA预防肺动脉血管收缩一致。所有这些结果表明，HSYA可能是治疗HPH的有前途的候选药物。
