内源性一氧化碳对低氧大鼠肺动脉胶原代谢的影响  

Effect of endogenous carbon monoxide on collagen metabolism of pulmonary artery of rats with hypoxia

作　　者：宫丽敏[1] 杜军保[1] 石云[1] 郭志良[1] 唐朝枢[2] 

机构地区：[1]北京大学第一医院儿科,北京100034 [2]北京大学第一医院心血管研究所,北京100034

出　　处：《基础医学与临床》2003年第5期490-493,共4页Basic and Clinical Medicine

基　　金：国家自然科学基金 (30 0 70 796 );国家重点基础研究项目 (G2 0 0 0 0 5 6 90 5 );北京市自然科学基金 (70 12 0 2 1)

摘　　要：探讨内源性一氧化碳 (CO)对低氧大鼠肺动脉胶原代谢的作用及其机制。采用常压低氧大鼠肺动脉高压模型 ,观察血红素加氧酶 (HO)抑制剂锌原卟啉 9(ZnPP 9)对肺动脉平均压 (PAMP)和肺组织匀浆碳氧血红蛋白 (Hb CO)含量的影响 ,并用免疫组织化学和核酸原位杂交法分别观察Ⅰ、Ⅲ型胶原蛋白的表达和肺动脉Ⅲ型前胶原[Proα1 (Ⅲ )胶原 ]mRNA、间质性胶原酶 (MMP 1)mRNA、金属蛋白酶组织抑制因子 1(TIMP)mRNA表达的变化。结果发现ZnPP 9使低氧大鼠PAMP明显升高 ,肺组织匀浆CO含量明显降低 ;ZnPP 9显著促进低氧大鼠肺动脉Ⅰ、Ⅲ型胶原蛋白表达 (P <0 0 1)和Proα1 (Ⅲ )胶原mRNA表达及MMP 1mRNA与TIMP 1mRNA表达 (P <0 0 1)。内源性CO可能通过抑制胶原蛋白的合成对低氧大鼠肺动脉胶原代谢发挥重要的调节作用。To explore the impact of endogenous carbon monoxide (CO) on collagen metabolism in pulmonary artery of rats with hypoxia. In the model of rats with hypoxic pulmonary hypertension the measurement of pulmonary artery mean pressure (PAMP) and carboxyhemoglobin (HbCO) formation within lung homogenates was performed. Collagen Ⅰand collagen Ⅲ expressions were detected by immunohistochemical assay. The expressions of type Ⅲ procollagen [Proα 1(Ⅲ) collagen] mRNA , interstitial collagenase (MMP 1) mRNA and tissue inhibitor of metalloproteinase (TIMP 1) mRNA were detected by in situ hybridization. ZnPP significantly increased PAMP and markedly decreased CO formation within lung homogenates in rats under hypoxia( P <0.01). Meanwhile, ZnPP promoted the expression of collagen Ⅰand collagen Ⅲ protein in pulmonary arteries in rats under hypoxia ( P <0.01). ZnPP elevated obviously the expressions of Proα 1 (Ⅲ) collagen mRNA, MMP 1 mRNA and TIMP 1 mRNA in pulmonary arteries in rats with hypoxia ( P <0.01). The data showed that endogenous CO played an important role in collagen metabolism in pulmonary artery of rats under hypoxia by inhibiting the synthesis of collagen.

关 键 词：内源性一氧化碳 低氧 大鼠 胶原代谢 锌原卟啉-9 肺动脉高压 

分 类 号：R363[医药卫生—病理学]