高碳酸血症通过赖氨酰氧化酶依赖的胶原蛋白交联影响大鼠缺氧性肺动脉高压

发布时间：2018-03-27 07:05

本文选题：缺氧　切入点：高碳酸血症　出处：《中国病理生理杂志》2017年08期

【摘要】：目的:通过研究缺氧和/或高碳酸血症时赖氨酰氧化酶(LOX)以及细胞外基质胶原蛋白的交联变化,探讨高碳酸血症对缺氧性肺动脉高压的影响机制。方法:SD大鼠随机均分为4组,分别为常氧对照组、缺氧组、高碳酸血症组以及缺氧+高碳酸血症组。比色法测定胶原蛋白含量,荧光光谱法分析LOX酶活性,免疫组织化学和Western blot法检测肺动脉LOX蛋白含量,实时荧光定量PCR检测肺动脉LOX的mRNA水平。结果:缺氧组大鼠平均肺动脉压(m PAP)、右心室/(左心室+室间隔)重量比值[RV/(LV+S)]及血管壁面积(WA)/血管总面积(TA)均明显高于常氧对照组;高碳酸血症组与常氧对照组的m PAP、RV/(LV+S)差异无统计学显著性;缺氧+高碳酸血症组大鼠的m PAP及RV/(LV+S)显著低于单纯缺氧组。缺氧组大鼠肺组织的胶原交联程度则明显高于常氧组及高碳酸血症组;高碳酸血症组大鼠肺组织的胶原交联程度与常氧组比较无显著差异;缺氧+高碳酸血症组大鼠肺组织的胶原交联程度显著低于缺氧组。缺氧组大鼠肺动脉LOX的mRNA、蛋白表达量及其酶活性均高于常氧组(P0.01);缺氧+高碳酸血症组大鼠肺动脉LOX mRNA、蛋白表达以及酶活性均明显低于缺氧组(P0.01)。结论:缺氧能诱导肺动脉LOX高表达,通过促进胶原合成及交联,参与肺动脉高压的形成。高碳酸血症通过抑制缺氧诱导的LOX表达和胶原交联,延缓缺氧性肺动脉高压的进展。
[Abstract]:Objective: to investigate the effects of hypercapnia on hypoxic pulmonary hypertension by studying the changes of lysyl oxidase LOX) and collagen in extracellular matrix during hypoxia and / or hypercapnia. Methods: the rats were randomly divided into 4 groups. The content of collagen was measured by colorimetric method, the activity of LOX enzyme was analyzed by fluorescence spectrometry, the content of LOX protein in pulmonary artery was detected by immunohistochemistry and Western blot. Results: the mean pulmonary artery pressure (MPP), the ratio of right ventricular / left ventricular septal weight [RV/(LV S] and the wall area of pulmonary artery in hypoxic group were significantly higher than those in normoxic control group. There was no significant difference between hypercapnia group and normoxic control group. The m PAP and RV/(LV S of hypoxic hypercapnia group were significantly lower than those of pure hypoxia group, while the degree of collagen cross-linking in hypoxic group was significantly higher than that in normoxic group and hypercapnia group. There was no significant difference in the degree of collagen cross-linking between hypercapnia group and normoxic group. The degree of collagen crosslinking in hypoxic hypercapnia group was significantly lower than that in hypoxia group, and the expression of LOX, protein expression and enzyme activity of pulmonary artery in hypoxia group were higher than those in normoxic hypercapnia group, and pulmonary motility in hypoxic hypercapnia group was higher than that in hypoxia hypercapnia group. The expression of LOX mRNAs, protein and enzyme activity were significantly lower than those in hypoxia group (P 0.01). Conclusion: hypoxia can induce high expression of LOX in pulmonary artery. Hypercapnia delays the development of hypoxic pulmonary hypertension by inhibiting hypoxia-induced LOX expression and collagen crosslinking.
【作者单位】：温州医科大学附属第二医院育英儿童医院呼吸内科;山东大学齐鲁医院呼吸内科;
【基金】：浙江省自然科学基金资助项目(No.LY12H01002) 温州市科技计划资助项目(No.2017Y0182)
【分类号】：R544.1

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