CTGF与低氧性肺血管重构的关系及波生坦的调控作用
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摘要
目的探讨结缔组织生长因子(CTGF)在低氧性肺动脉高压(HPH)大鼠肺内的表达及波生坦的调控作用。方法用全自动调节的低压低氧舱复制HPH大鼠模型,采用免疫组化法检测各组大鼠肺内CTGF蛋白表达,并经图像分析半定量检测其表达强度。结果实验结果发现CTGF在对照组大鼠的肺小动脉壁、支气管上皮细胞和肺泡内皮细胞有基础量的表达,且低氧3周组及安慰剂组肺动脉CTGF的表达显著增多;波生坦干预后肺小动脉壁CTGF蛋白表达显著降低。结论 CTGF与HPH肺血管重构密切相关;波生坦下调CTGF表达可能是其改善肺血管重构的重要机制之一。
Objective To explore the expression of connective tissue growth factor(CTGF) in the lung tissues of chronic hypoxic pulmonary hypertension(HPH) rats, and investigate the regulation of CTGF expression by bosentan. Methods Low pressure and low oxygen chamber was used to establish HPH rat model, and the expression of CTGF in rat lungs were measured by immunohistochemical staining, then its expression intensity was given semi-quantitative detection by image analysis. Results It was found that CTGF had basic expression in pulmonary arterioles, bronchial epithelial cells and alveolar endothelial cells of rats in the control group. The expression of CTGF in pulmonary artery increased significantly in hypoxia 3 weeks group and placebo group, and decreased significantly in pulmonary artery wall after bosentan intervention. Conclusion CTGF is closely related to pulmonary vascular remodeling in HPH, and the down-regulation of CTGF expression by bosentan may be one of the important mechanisms of improving pulmonary vascular remodeling.
Objective To explore the expression of connective tissue growth factor(CTGF) in the lung tissues of chronic hypoxic pulmonary hypertension(HPH) rats, and investigate the regulation of CTGF expression by bosentan. Methods Low pressure and low oxygen chamber was used to establish HPH rat model, and the expression of CTGF in rat lungs were measured by immunohistochemical staining, then its expression intensity was given semi-quantitative detection by image analysis. Results It was found that CTGF had basic expression in pulmonary arterioles, bronchial epithelial cells and alveolar endothelial cells of rats in the control group. The expression of CTGF in pulmonary artery increased significantly in hypoxia 3 weeks group and placebo group, and decreased significantly in pulmonary artery wall after bosentan intervention. Conclusion CTGF is closely related to pulmonary vascular remodeling in HPH, and the down-regulation of CTGF expression by bosentan may be one of the important mechanisms of improving pulmonary vascular remodeling.
引文
[1]杨诚忠,李满满,罗羽莎,等.LIGHT在低氧性肺动脉高压形成中的作用及机制[J].第三军医大学学报,2018,40(8):643-651.
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[9]张存娟,杨瑞,邢文娟,等.脂联素改善间歇性低氧性肺动脉高压大鼠离体肺动脉舒张功能及其机制[J].心脏杂志,2016,28(3):273-278.
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[11]王英,李亚,李建生.慢性阻塞性肺疾病肺血管重塑研究进展[J].中医学报,2012,27(2):143-145.
[12]梁潇.低压低氧时细胞因子的变化特点及其与心肌纤维化的关系[D].重庆:重庆医科大学,2016.
[13]冯迎军.先天性心脏病合并肺动脉高压患者的心肌纤维化评价[J].山东医药,2016,56(5):32-34.
[14]刘斌,王献民,周同甫,等.大鼠肺动脉高压模型结缔组织生长因子的表达及辛伐他汀的调控作用[J].中华儿科杂志,2008,46(5):359-365.
[15]付杰,卢翠侠,李刚,等.结缔组织生长因子-整合素β受体信号途径在肺动脉平滑肌细胞增殖和迁移中的作用[J].中华实用儿科临床杂志,2014,29(13):1005-1009.
[16]张永锋,郑毅.结缔组织生长因子和肺动脉高压[J].中华风湿病学杂志,2010,14(3):199-201.
[17]冀璐.结缔组织生长因子在先天性心脏病合并肺动脉高压中的表达和意义[D].太原:山西医科大学,2015.
[18]徐晶,张玉顺,宋强,等.安立生坦与波生坦对低氧性肺动脉高压大鼠右心室重构影响的比较研究[J].心脏杂志,2013,25(3):257-261.
[2] MICHELAKIS ED,MCMURTRY MS,WU XC,et al.Dichloroacetate, a metabolic modulator, prevents and reverses chronic hypoxic pulmonary hypertension in rats:role of increased expression and activity of voltage-gated potassium channels[J].Circulation,2002,105(2):244-250.
[3] SOMA S,TAKAHASHI H,MURAMATSU M,et al.Localization and distribution of endothelin receptor subtypes in pulmonary vasculature of normal and hypoxia-exposed rats[J].Am J Respir Cell Mol Biol,1999,20(4):620-630.
[4] KONDO S,KUBOTA S,SHIMO T,et al.Connective tissue growth factor increased by hypoxia may initiate angiogenesis in collaboration with matrix metalloproteinases[J].Carcinogenesis,2002,23(5):769-776.
[5] KEEGAN A,MORECROFT I,SMILLIE D,et al.Contribution of the 5-HT(1B)receptor to hypoxia-induced pulmonary hypertension:converging evidence using 5-HT(1B)-receptor knockout mice and the5-HT(1B/1D)-receptor antagonist GR127935[J].Circ Res,2001,89(12):1231-1239.
[6] DORMOWICZ AG, STENMARY KR. Mechanisms of structural remodeling in chronic pulmonary hypertension[J].Pediatr Rev,1999,20(11):e91-e102.
[7] BRADHAM DM,IGARASHI A,POTTER RL,et al.Connective tissue growth factor:a cysteine-rich mitogen secreted by human vascular endothelial cells is related to the SRC-induced immediate early gene product CEF-10[J].J Cell Biol,1991,114(6):1285-1294.
[8] SHIMO T,KUBOTA S,KONDO S,et al.Connective tissue growth factor as a major angiogenic agent that is induced by hypoxia in a human breast cancer cell line[J].Cancer Lett,2001,174(1):57-64.
[9]张存娟,杨瑞,邢文娟,等.脂联素改善间歇性低氧性肺动脉高压大鼠离体肺动脉舒张功能及其机制[J].心脏杂志,2016,28(3):273-278.
[10]冀璐,李亚蕊.先天性心脏病及合并肺动脉高压患儿血清结缔组织生长因子表达的意义[J].中华实用儿科临床杂志,2015,30(1):38-40.
[11]王英,李亚,李建生.慢性阻塞性肺疾病肺血管重塑研究进展[J].中医学报,2012,27(2):143-145.
[12]梁潇.低压低氧时细胞因子的变化特点及其与心肌纤维化的关系[D].重庆:重庆医科大学,2016.
[13]冯迎军.先天性心脏病合并肺动脉高压患者的心肌纤维化评价[J].山东医药,2016,56(5):32-34.
[14]刘斌,王献民,周同甫,等.大鼠肺动脉高压模型结缔组织生长因子的表达及辛伐他汀的调控作用[J].中华儿科杂志,2008,46(5):359-365.
[15]付杰,卢翠侠,李刚,等.结缔组织生长因子-整合素β受体信号途径在肺动脉平滑肌细胞增殖和迁移中的作用[J].中华实用儿科临床杂志,2014,29(13):1005-1009.
[16]张永锋,郑毅.结缔组织生长因子和肺动脉高压[J].中华风湿病学杂志,2010,14(3):199-201.
[17]冀璐.结缔组织生长因子在先天性心脏病合并肺动脉高压中的表达和意义[D].太原:山西医科大学,2015.
[18]徐晶,张玉顺,宋强,等.安立生坦与波生坦对低氧性肺动脉高压大鼠右心室重构影响的比较研究[J].心脏杂志,2013,25(3):257-261.