补阳还五汤通过改善线粒体功能抑制高血压所致肾脏损害的机制研究

目前公认，单核/巨噬细胞（Mφ）介导的炎症反应诱发和促进高血压所致肾损害的发生和发展。线粒体除了与能量代谢相关外，新近研究显示，线粒体功能下降及其介导产生的活性氧（ROS）还与炎症反应的发生密切相关。中医学认为气虚血瘀常为高血压肾病的基本病机。我们发现益气活血的代表方补阳还五汤（BYHW）抑制高血压大鼠的肾损害，但机制不明。BYHW重用黄芪，研究表明黄芪可改善线粒体功能。为此，本课题将在高血压动物模型上，通过利用特异性的线粒体ROS清除剂mitoTEMPO，明确BYHW的肾脏保护是通过抑制线粒体ROS的产生减轻Mφ介导的炎症反应。另外，通过血管内皮细胞和Mφ培养模型，探明BYHW对线粒体功能的改善作用，以及该作用对Mφ的粘附、溢出、移动和功能表型（M1、M2）的影响。因此，本课题将首次阐明BYHW通过改善线粒体功能抑制Mφ介导的炎症反应，从而揭示BYHW抑制高血压所致肾损害的药理学机制。

It is well accepted that monocyte/macrophage-mediated inflammation promotes the development of hypertension-induced renal injury. In addition to mitochondria involved in energy metabolism, recent studies have shown that mitochondrial dysfunction and its reactive oxygen species (ROS) contribute to pathogenesis of inflammation. Following traditional Chinese medicine (TCM) theory, Qi deficiency and blood stasis syndrome is the principal TCM syndrome in the pathogenesis of hypertensive nephropathy. We found that Buyang Huanwu Decoction (BYHWD), a representative prescription of Qi-tonifying and stasis-eliminating method, attenuated renal injury in hypertensive rats, but the mechanisms are not elucidated. The main characteristic of BYHWD is the use of principal drug Radix Astragali (huang qi) in large dose, Radix Astragali is reported to improve mitochondria. Therefore, in an animal model of hypertension, we will elucidate whether BYHWD provides renal protection via attenuating mitochondrial ROS to reduce monocyte/macrophage-mediated inflammation using a specific scavenger of mitochondrial ROS (mitoTEMPO). Moreover, using a vitro culture model of endothelial cell and macrophage, we will clarify the ameliorating effects of BYHWD on mitochondrial function, and its effects on monocyte/macrophage attachment, transmigration, migration, and macrophage polarization (M1 and M2). So our studies will firstly demonstrate that BYHWD attenuates monocyte/macrophage-mediated inflammation via improving mitochondrial function, which constitutes the pharmacological mechanisms by which BYHWD attenuates renal injury in hypertension.