Upregulation of Transient Receptor Potential Canonical Channels Contributes to Endotoxin-Induced Pulmonary Arterial Stenosis.
Upregulation of Transient Receptor Potential Canonical Channels Contributes to Endotoxin-Induced Pulmonary Arterial Stenosis.
复制标题
瞬时受体电位经典通道的上调导致内毒素诱导的肺动脉狭窄
DOI：
10.12659/msm.898111
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发表时间：
2016-07-29
期刊：
影响因子：
--
通讯作者：
Zou F
中科院分区：
文献类型：
--
作者：
Chen GL;Jiang H;Zou F
背景感染性休克是由内毒素产生菌引起的一种病理状态，常伴有严重的肺动脉高压。炎症是对内毒素的一种主要的全身反应；然而，目前尚不清楚内毒素是否直接影响了肺动脉，从而导致了肺动脉高压的发生。材料/方法体外培养大鼠肺动脉和原代培养的肺动脉平滑肌细胞(PASMC)，用脂多糖(LPS)和瞬时受体潜伏期通道阻断剂(TRPC)进行处理。培养的肺动脉冰冻切片可见新生内膜生长和动脉狭窄。用WST-1法检测PASMCs的增殖情况。采用实时定量聚合酶链式反应和Western blotting方法检测并定量检测大鼠肺动脉和PASMCs中TRPC基因的表达。结果内毒素可明显促进PASMCs的增殖，增加新生血管内膜的形成和狭窄程度。TRPC通道阻断剂2-氨基乙氧基二苯基硼酸酯和SKF-96365可抑制脂多糖诱导的肺动脉重塑和PASMC增殖。TRPC1/3/4/6在肺动脉和PASMCs均有表达。LPS处理显著增加了TRPC3和TRPC4在信使RNA和蛋白质水平上的表达。结论脂多糖通过促进TRPC介导的钙离子进入PASMCs，导致TRPC3和TRPC4通道上调，从而刺激肺动脉狭窄。
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/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.