CAJ | 학술논문

低氧可以诱发肺动脉高压,低氧环境下血管平滑肌增生和肥大导致的血管重塑是肺动脉高压的重要因素.因此研究血管平滑肌增生和肥大发生的原因、进程、以及如何抑制平滑肌的增生对低氧性肺动脉高压的预防和治疗具有重要的意义.本研究以NF-κB为研究目标,采用药物干预及基因敲除策略证明了NF-κB在低氧性肺动脉高压中被活化,而且NF-κB的抑制剂-穿心莲内酯具有延缓肺动脉高压进程的作用.
저양가이유발폐동맥고압,저양배경하혈관평활기증생화비대도치적혈관중소시폐동맥고압적중요인소.인차연구혈관평활기증생화비대발생적원인、진정、이급여하억제평활기적증생대저양성폐동맥고압적예방화치료구유중요적의의.본연구이NF-κB위연구목표,채용약물간예급기인고제책략증명료NF-κB재저양성폐동맥고압중피활화,이차NF-κB적억제제-천심련내지구유연완폐동맥고압진정적작용.
Chronic hypoxia induces pulmonary arterial hypertension (PAH). Smooth muscle cell (SMC) proliferation and hypertrophy are important contributors to the remodeling that occursin chronic hypoxic pulmonary vasculature. The NF-κB transcription factors modulate the expression of tissue factor (TF), E-selectin (CD62E) and vascular cell adhesion molecule-1 (VCAM-1), which are essential for the arterial remodeling. andrographolide (Andro) covalently modifies the reduced cysteine62 of p50-am ajor subunit of NF-κB transcription factors, thus blocking the binding of NF-κB transcription factors to the promoters of their target genes, preventing NF-κB activation and inhibiting inflammation in vitro and in vivo. Here we report that Andro,but not its inactive structural analog 4H-Andro, significantly suppressed hypoxia-induced pulmonary hypertension in a murine model. Consistently, p50-/- mice manifested attenuated the same results. Our data thus indicate that, by the inhibition of the NF-κB that are important in thrombosis and inflammation,specific inhibitors of p50, such as Andro, may be therapeutically valuable for preventing and treating hypoxia-induced pulmonary hypertension.