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目的:探究骨形成蛋白4(BMP4)在血小板源性生长因子(PDGF)诱导的肺动脉重塑中的作用及其机制。方法:本研究为实验研究。使用细胞活力检测、蛋白活力测定、蛋白质印迹法、siRNA干扰技术等方法研究BMP4对肺动脉平滑肌细胞(PASMC)的作用。烟雾连续暴露12周小鼠构建肺动脉重塑的动物模型，免疫荧光检测肺动脉BMP4的表达。结果:相较于PDGF组，PDGF+BMP4组能够抑制Ⅰ型胶原蛋白的合成(n P<0.001)和钙蛋白酶活性(n P<0.001)。相较于对照组，蛋白激酶A(PKA)的活性增加(n P<0.001)。已知PKA是钙蛋白酶活性的负调控因子。使用PKA激活剂后，PDGF诱导的钙蛋白酶活性下降(n P<0.01)。siRNA沉默PKA，由BMP4下调的钙蛋白酶活性得以恢复(n P<0.001)，并增加了Ⅰ型胶原蛋白的表达量(n P<0.001)。与PDGF组相比，PDGF+BMP4抑制转化生长因子βn 1(TGF-βn 1)的活化(n P<0.001)和Smad2/3的磷酸化(n P<0.001)。在烟雾暴露的小鼠肺动脉中，BMP4蛋白表达降低(n P<0.001)。n 结论:BMP4通过激活PKA抑制钙蛋白酶-TGF-βn 1信号轴，导致PASMC Ⅰ型胶原蛋白合成下降。BMP4作为一种保护因素阻碍肺动脉重塑。n “,”Objective:To explores the effects and mechanism of bone morphogenetic protein 4 (BMP4) in platelet-derived growth factor (PDGF)-induced pulmonary artery remodeling.Methods:This is an experimental study.The effects of BMP4 on pulmonary artery smooth muscle cells (PASMC) were investigated by cell viability assay, protein viability assay, western blotting, and siRNA interference technology.The mice were exposed to smoke for 12 weeks to set up an animal model of pulmonary artery remodeling, and the expression of BMP4 in the pulmonary artery was detected by immunofluorescence.Results:The synthesis of collagen type Ⅰ (n P<0.001) and calpain activity (n P<0.001) could be inhibited in the PDGF+ BMP4 group compared with PDGF group.The activity of protein kinase A (PKA) increased (n P<0.001) compared with the control group.PKA had been known to be a negative regulator of calpain activity.PDGF-induced calpain activity decreased after PKA activator (n P<0.01). siRNA silencing of PKA restored calpain activity down-regulated by BMP4 (n P<0.001), and increased the expression collagen type Ⅰ (n P<0.001); PDGF+ BMP4 inhibited the activation of transforming growth factor-βn 1 (TGF-βn 1)(n P<0.001) and the phosphorylation of Smad2/3 (n P<0.001) compared with the PDGF group.BMP4 protein expression decreased in the pulmonary arteries of smoke-exposed mice (n P<0.001).n Conclusions:BMP4 inhibits the calpain-TGF-βn 1 signaling axis by activating PKA, causing the decrease of type Ⅰ collagen synthesis in PASMC.BMP4 acts as a protective factor blocking pulmonary artery remodeling.n