骨形成蛋白2调节肺动脉高压肺血管重构的作用机制研究  

The mechanism of bone morphogenetic protein 2 regulating pulmonary vascular remodeling in pulmonary hypertension

作　　者：麦静仪[1] 饶晓林 蔡勇[2] 林舜娜 Mai Jingyi;Rao Xiaolin;Cai Yong;Lin Shunna(Department of Pediatrics,Guangzhou Twelfth People′s Hospital,Guangzhou 510620,China;Department of Pediatrics,the First Affiliated Hospital of Guangzhou Medical University,Guangzhou 510405,China;Department of Pediatrics,Guangzhou Tianhe District Maternal and Child Health and Family Planning Service Center,Guangzhou 510610,China)

机构地区：[1]广州市第十二人民医院儿科,广州510620 [2]广州医科大学附属第一医院儿科,广州510405 [3]广州市天河区妇幼保健计划生育服务中心儿科,广州510610

出　　处：《中国医师进修杂志》2023年第8期763-768,共6页Chinese Journal of Postgraduates of Medicine

基　　金：广东省医学科学技术研究基金(B2022187)。

摘　　要：目的探讨骨形成蛋白2(BMP-2)调节肺动脉高压(PH)肺血管重构的作用机制。方法肺动脉平滑肌细胞(PASMC)分组:对照组、PH组、PH+BMP-2组、PH+BMP-2+小干扰BMP-2受体(si-BMPR)-Ⅰa组、PH+BMP-2+si-BMPR-Ⅰb组、PH+BMP-2+si-BMPR-Ⅱ组。通过缺氧诱导体外PH模型,分别转染si-BMPR-Ⅰa、si-BMPR-Ⅰb、si-BMPR-Ⅱ质粒沉默BMP-2的3个受体。检测各组细胞增殖、凋亡情况,检测瞬时受体电位离子通道C1/6(TRPC1/6)、p21 mRNA和蛋白水平,以及细胞内钙离子水平。结果PH组PASMC中钙离子水平高于对照组[(785.15±44.26)nmol/L比(224.15±15.87)nmol/L],而凋亡率低于对照组[(3.15±0.22)%比(7.31±0.45)%],差异有统计学意义(P<0.05);PH+BMP-2组钙离子水平(297.64±21.46)nmol/L,低于PH组,而凋亡率为(6.88±0.75)%,高于PH组,差异有统计学意义(P<0.05);PH+BMP-2+si-BMPR-Ⅰa组、PH+BMP-2+si-BMPR-Ⅰb组和PH+BMP-2+si-BMPR-Ⅱ组钙离子水平分别为(412.31±29.57)、(384.34±30.66)、(695.23±39.85)nmol/L,均高于PH+BMP-2组,而凋亡率分别为(4.10±0.27)%、(4.26±0.28)%、(3.33±0.24)%,均低于PH+BMP-2组,差异有统计学意义(P<0.05),其中PH+BMP-2+si-BMPR-Ⅱ组钙离子水平高于PH+BMP-2+si-BMPR-Ⅰa组和PH+BMP-2+si-BMPR-Ⅰb组,而凋亡率低于PH+BMP-2+si-BMPR-Ⅰa组和PH+BMP-2+si-BMPR-Ⅰb组,差异有统计学意义(P<0.05)。结论BMP-2主要通过与受体BMPR-Ⅱ作用抑制TRPC1/6的表达,并抑制钙离子内流和促进p21表达,从而抑制PASMC的增殖并促进凋亡,参与肺血管重构。Objective To explore the mechanism of bone morphogenetic protein 2(BMP-2)regulating pulmonary vascular remodeling in pulmonary hypertension(PH).Methods Pulmonary artery smooth muscle cells(PASMC)groups:control group,PH group,PH+BMP-2 group,PH+BMP-2+small interfering BMP receptor(si-BMPR)-Ⅰa group,PH+BMP-2+si-BMPR-Ⅰb group,PH+BMP-2+si-BMPR-Ⅱgroup.In vitro PH model was induced by hypoxia.The three BMP-2 receptors were silenced by the transfection of si-BMPR-Ⅰa,si-BMPR-Ⅰb and si-BMPR-Ⅱplasmids,respectively.Cell proliferation and apoptosis in each group were detected,transient receptor potential ion channel C1/6(TRPC1/6),p21 mRNA and protein levels,and intracellular Ca2+concentration were detected.Results The intracellular Ca2+concentration in the PH group was higher than that in the control group:(785.15±44.26)nmol/L vs.(224.15±15.87)nmol/L,the and apoptosis rate was lower than that in the control group:(3.15±0.22)%vs.(7.31±0.45)%,there were statistical differences(P<0.05).The intracellular Ca2+concentration in the PH+BMP-2 group was(297.64±21.46)nmol/L,and was lower than that in the PH group,and apoptosis rate was(6.88±0.75)%,and was higher than that in the PH group,there were statistical differences(P<0.05).The intracellular Ca2+concentration in the PH+BMP-2+si-BMPR-Ⅰa group,PH+BMP-2+si-BMPR-Ⅰb group,PH+BMP-2+si-BMPR-Ⅱgroup was(412.31±29.57),(384.34±30.66),(695.23±39.85)nmol/L,and was higher than that in the PH+BMP-2 group,and apoptosis rate was(4.10±0.27)%,(4.26±0.28)%,(3.33±0.24)%,and was lower than that in the PH+BMP-2 group,there were statistical differences(P<0.05).The intracellular Ca2+concentration in the PH+BMP-2+si-BMPR-Ⅱgroup was higher than that in the PH+BMP-2+si-BMPR-Ⅰa group and PH+BMP-2+si-BMPR-Ⅰb group,the apoptosis rate was lower than that in the PH+BMP-2+si-BMPR-Ⅰa group and PH+BMP-2+si-BMPR-Ⅰb group,there were statistical differences(P<0.05).Conclusions BMP-2 mainly inhibits the expression of TRPC1/6 by interacting with the receptor BMPR-Ⅱ,inhibits the i

关 键 词：肺动脉高压 血管重构 骨形成蛋白2 细胞增殖 细胞凋亡 

分 类 号：R544.1[医药卫生—心血管疾病]