Chen Gui-Lan, Jiang Hongni, Zou Fangdong
Ministry of Education Key Laboratory of Bio-Resources and Eco-Environment, College of Life Sciences, Sichuan University, Chengdu, Sichuan, China (mainland).
Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University School of Medicine, Shanghai, China (mainland).
Med Sci Monit. 2016 Jul 29;22:2679-84. doi: 10.12659/msm.898111.
BACKGROUND Septic shock is a pathologic condition caused by endotoxin-producing bacteria, and often associated with severe pulmonary hypertension. Inflammation is a major systemic response to endotoxin; however, it is unknown whether endotoxin has a direct impact on pulmonary arteries that contributes to pathogenesis of pulmonary hypertension. MATERIAL AND METHODS Rat pulmonary arteries and primary pulmonary arterial smooth muscle cells (PASMCs) were cultured in vitro and treated with lipopolysaccharide (LPS) and blockers of transient receptor potential canonical (TRPC) channels. Neointimal growth and arterial stenosis were observed on cryosections of cultured pulmonary arteries. Proliferation of PASMCs was examined by a WST-1 (water-soluble tetrazolium salt) assay. Expression of TRPC genes in pulmonary arteries and PASMCs were detected and quantified by real-time polymerase chain reaction and Western blotting. RESULTS LPS significantly induced neointimal growth and stenosis of pulmonary arteries and promoted proliferation of PASMCs. TRPC channel blockers 2-aminoethoxydiphenyl borate and SKF-96365 inhibited LPS-induced remodeling of pulmonary arteries and PASMC proliferation. Expression of TRPC1/3/4/6 was detected in pulmonary arteries and PASMCs. LPS treatment dramatically increased the expression of TRPC3 and TRPC4 at both messenger RNA and protein levels. CONCLUSIONS LPS stimulates stenosis of pulmonary arteries through enhancement of TRPC-mediated Ca2+ entry into PASMCs, which is caused by upregulation of TRPC3 and TRPC4 channels.
脓毒性休克是一种由产生内毒素的细菌引起的病理状态，常伴有严重的肺动脉高压。炎症是对内毒素的主要全身反应；然而，内毒素是否对肺动脉有直接影响并导致肺动脉高压的发病机制尚不清楚。
体外培养大鼠肺动脉和原代肺动脉平滑肌细胞（PASMCs），并用脂多糖（LPS）和瞬时受体电位香草酸亚型（TRPC）通道阻滞剂进行处理。在培养的肺动脉冰冻切片上观察内膜增生和动脉狭窄。通过WST-1（水溶性四氮唑盐）试验检测PASMCs的增殖情况。通过实时聚合酶链反应和蛋白质印迹法检测并定量肺动脉和PASMCs中TRPC基因的表达。
LPS显著诱导肺动脉内膜增生和狭窄，并促进PASMCs的增殖。TRPC通道阻滞剂2-氨基乙氧基二苯硼酸酯和SKF-96365抑制LPS诱导的肺动脉重塑和PASMC增殖。在肺动脉和PASMCs中检测到TRPC1/3/4/6的表达。LPS处理显著增加了TRPC3和TRPC4在信使核糖核酸和蛋白质水平的表达。
LPS通过增强TRPC介导的Ca2+进入PASMCs刺激肺动脉狭窄，这是由TRPC3和TRPC4通道上调引起的。
