内源性一氧化碳对低氧大鼠肺动脉转化生长因子-β_3和Ⅰ型胶原表达的影响  

Effects of endogenous carbon monoxide on the expression of transforming growth factor-beta 3 and type Ⅰ collagen of pulmonary artery in rats under hypoxia

作　　者：宫丽敏[1] 杜军保[1] 石云[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：《中国病理生理杂志》2003年第11期1441-1444,U001,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目 (No .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资助项目 (70 12 0 2 1)

摘　　要：目的 :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。方法 :采用常压低氧大鼠肺动脉高压模型 ,观察血红素氧合酶 (HO)抑制剂锌原卟啉 -Ⅸ (ZnPP -Ⅸ )对肺动脉平均压 (PAMP)和肺组织匀浆碳氧血红蛋白 (HbCO)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ZnPP -Ⅸ对肺动脉转化生长因子 - β3 (TGF - β3 )、Ⅰ型胶原蛋白的表达和肺动脉TGF - β3 mRNA、Ⅰ型前胶原mRNA和金属蛋白酶组织抑制因子 (TIMP - 1)mRNA表达的影响。结果 :ZnPP -Ⅸ使低氧大鼠PAMP明显升高 ,肺组织匀浆CO含量明显降低 ;ZnPP -Ⅸ能促进TGF - β3 蛋白表达和TGF - β3 mRNA表达 ,显著促进低氧大鼠肺动脉Ⅰ型胶原蛋白表达和Ⅰ型前胶原mRNA表达 ,上调TIMP - 1mRNA的表达。结论 :内源性CO可能通过抑制TGF - β3mRNA和TGF - β3 蛋白表达而抑制胶原蛋白的合成 ,促进胶原的降解 ,从而对低氧大鼠肺动脉胶原代谢发挥重要的调节作用。AIM: To explore the impact of endogenous carbon monoxide (CO) on the expression of transforming growth factor-beta 3 (TGF-β_3) and type Ⅰcollagen in pulmonary artery of rats under hypoxia. METHODS: In the model of rats under hypoxic pulmonary hypertension,the measurement of pulmonary artery mean pressure (PAMP) and carboxyhemoglobin (HbCO) formation within pulmonary tissue homogenates was performed. TGF-β_3 and collagen Ⅰexpressions were detected by immunohistochemical assay. The expressions of TGF-β_3,type Ⅰ procollagen mRNA,and tissue inhibitor of metalloproteinase -1 (TIMP-1) mRNA were detected by in situ hybridization. RESULTS: ZnPP significantly increased PAMP and markedly decreased HbCO formation within lung tissue homogenates in rats under hypoxia( P< 0.01). Meanwhile,ZnPP promoted the expression of TGF-β_3 and collagen Ⅰprotein in pulmonary arteries in rats under hypoxia ( P< 0.01). ZnPP obviously elevated the expressions of TGF-β_3 mRNA,type Ⅰ procollagen mRNA,and TIMP-1 mRNA in pulmonary arteries in rats under hypoxia ( P< 0.01). CONCLUSION: Endogenous CO plays an important role in decreasing collagen synthesis and promoting degradation in pulmonary artery of rats under hypoxia by inhibiting the expression of TGF-β_3.

关 键 词：一氧化碳 缺氧大鼠 肺动脉胶原代谢 转化生长因子Β Ⅰ型胶原蛋白 蛋白表达 慢性缺氧性肺动脉高压 

分 类 号：R543.2[医药卫生—心血管疾病]