Effects of baicalin on collagen I and collagen III expression in pulmonary arteries of rats with hypoxic pulmonary hypertension
Effects of baicalin on collagen I and collagen III expression in pulmonary arteries of rats with hypoxic pulmonary hypertension
复制标题
黄芩苷对缺氧性肺动脉高压大鼠肺动脉Ⅰ型胶原和Ⅲ型胶原表达的影响
DOI：
10.3892/ijmm.2015.2110
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发表时间：
2015-04-01
影响因子：
5.4
通讯作者：
Huang, Xiaoying
中科院分区：
文献类型：
--
作者：
Liu, Panpan;Yan, Shuangquan;Huang, Xiaoying
胶原的合成和积累在低氧性肺动脉高压的形成和发展中起重要作用。黄芩苷已被报道可预防博来霉素诱导的肺纤维化。然而，黄芩苷在治疗肺动脉高压中的作用仍然未知。具有血小板反应蛋白1型基序的去整合素和金属蛋白酶（ADAMTS-1）是一种分泌酶，其作用于与血管疾病相关的多种细胞外基质（ECM）底物。本研究旨在探讨黄芩苷对缺氧性肺动脉高压大鼠I型胶原合成及ADAMTS-1表达的影响。将24只SD道利大鼠随机分为3组：对照组（C）、缺氧组（H）和缺氧+黄芩苷组（B）。H组和B组置于常压低氧舱中4周，C组暴露于室内空气中。测定血流动力学指标，包括平均肺动脉压（mPAP）、平均体循环（颈动脉）动脉压（mSAP），计算右心室与左心室加室间隔的质量比[RV/（LV + S）]，以反映右心室肥厚程度。我们分别通过原位杂交、免疫组化和western blot分析来检测I型胶原、III型胶原和ADAMTS-1的mRNA和蛋白表达水平。结果表明，黄芩苷通过增加ADAMTS-1的表达，抑制I型胶原的合成及其mRNA的表达，从而显著降低肺动脉压，减轻缺氧条件下肺动脉重构。总之，黄芩苷有效抑制肺动脉I型胶原的合成，这与ADAMTS-1表达的增加有关。因此，黄芩苷治疗可能是降低肺动脉压和预防肺动脉重构的有效方法。
The synthesis and accumulation of collagen play an important role in the formation and progression of hypoxic pulmonary hypertension. Baicalin has been reported to prevent bleomycin-induced pulmonary fibrosis. However, the role of baicalin in the treatment of pulmonary hypertension remains unknown. A disintegrin and metalloprotease with thrombospondin type-1 motif (ADAMTS-1) is a secreted enzyme that acts on a wide variety of extracellular matrix (ECM) substrates associated with vascular diseases. In this study, we aimed to investigate the effects of baicalin on the synthesis of collagen I in rats with pulmonary hypertension induced by hypoxia and the changes in ADAMTS-1 expression. A total of 24 Sprague Dawley rats were randomly assigned to 3 groups as follows: the control group (C), the hypoxia group (H) and the hypoxia + baicalin group (B). The rats in groups H and B were kept in a normobaric hypoxic chamber for 4 weeks, and the rats in group C were exposed to room air. We measured the hemodynamic indexes, including mean pulmonary artery pressure (mPAP), mean systemic (carotid) artery pressure (mSAP), and then calculated the mass ratio of right ventricle to left ventricle plus septum [RV/(LV + S)] to reflect the extent of right ventricular hypertrophy. We measured the mRNA and protein expression levels of type I collagen, type III collagen and ADAMTS-1 by hybridization in situ, and immunohistochemistry and western blot analysis, respectively. The results revealed that treatment with baicalin significantly reduced pulmonary artery pressure and attenuated the remodeling of the pulmonary artery under hypoxic conditions by increasing the expression of ADAMTS-1, so that the synthesis of type I collagen and its mRNA expression were inhibited. In conclusion, baicalin effectively inhibits the synthesis of collagen I in pulmonary arteries and this is associated with an increase in the expression of ADAMTS-1. Thus, treatment with baicalin may be an effective method for lowering pulmonary artery pressure and preventing pulmonary artery remodeling.