穿心莲内酯抑制缺氧性肺动脉高压的实验研究  

The experimental study of andrographolide attenuating hypoxia-induced pulmonary hypertension in a mouse model

作　　者：王玉玖[1] 王晶[2] 李伟[1] 董圣军[1] 封赞祥[1] 刘典晓[1] 

机构地区：[1]山东省滨州医学院心脏外科,256603 [2]滨州医学院口腔内科

出　　处：《中国临床实用医学》2010年第4期124-127,共4页China Clinical Practical Medicine

摘　　要：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。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 hyperten- sion 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.

关 键 词：穿心莲内酯 肺动脉高压 核因子-κB组织因子 

分 类 号：R544[医药卫生—心血管疾病]