HO-1/CO轴通过Nrf2信号通路对血管再狭窄的抑制作用机制研究

Restenosis (RS) is a major complication for percutaneous transluminal angioplasty (PTA) treatment. RS severely cripples prognosis of RS and it is vital to explore the mechanism of RS development and progression. For now, the molecular mechanisms of PTA induced RS have not been fully elucidated, but it is believed that oxidative stress may be involved in this process. Carbon monoxide and heme oxygenase-1 (CO/HO-1) axis , consisting of this gaseous signal molecule together with its generation-limiting enzyme and various products , plays a vital role in cardiovascular disease treatment. But whether CO/HO-1 axis can inhibit the occurrence and development of RS after PTA remains unknown. Our pre-studies showed that CO/HO-1 axis significantly restrained RS by inhibiting oxidative reaction, and this protective property was tightly connected with Nrf2 signal transduction pathway. In this study, from in vivo and in vitro level, we explore whether CO/HO-1 axis affects Nrf2 signal transduction pathway, and increases antioxidant protein level to clear oxygen free radical, lower oxidative stress, down-regulate NF- kappa B and pro-inflammatory cytokines expression, and finally cease the occurrence and progression of RS after PTA. We also try to find a novel and effective pharmacological target to cure RS after PTA.

血管再狭窄（Restenosis RS）是经皮腔内血管成形术（PTA）后主要并发症之一，严重影响预后，探究RS的发生机制尤为重要。氧化应激可能与RS的发生有关。前期发现，一氧化碳（CO）及血红素加氧酶-1轴（CO/HO-1轴）在抗心血管疾病中起重要调控作用，但尚无研究表明CO/HO-1轴能否抑制PTA术后RS的发生发展。预实验显示，CO可通过抑制氧化应激反应减轻RS，而这种保护作用与Nrf2通路密切相关，但具体机制尚未明确。故本项目拟从整体动物和离体细胞水平，探讨CO/HO-1轴是否通过影响Nrf2信号通路的转导，引起下游抗氧化蛋白水平升高，进而有效清除氧自由基、降低氧化应激水平、抑制NF-κB及相关炎症因子的激活及释放，抑制PTA术后RS的发生发展。

血管再狭窄(Restenosis RS)是经皮腔内血管成形术(PTA)后主要并发症之一，严重 影响预后，探究RS的发生机制尤为重要。氧化应激可能与RS的发生有关。前期发现，一氧化碳 (CO)及血红素加氧酶-1轴(CO/HO-1轴)在抗心血管疾病中起重要调控作用，但尚无研究表 明CO/HO-1轴能否抑制PTA术后RS的发生发展。预实验显示，CO可通过抑制氧化应激反应减轻RS ，而这种保护作用与Nrf2通路密切相关，但具体机制尚未明确。故本项目拟从整体动物和离体 细胞水平，探讨CO/HO-1轴是否通过影响Nrf2信号通路的转导，引起下游抗氧化蛋白水平升高 ，进而有效清除氧自由基、降低氧化应激水平、抑制NF-κB及相关炎症因子的激活及释放，抑 制PTA术后RS的发生发展。