硫化氢对低氧大鼠肺动脉金属蛋白酶组织抑制因子-1基因表达的影响

目的 研究硫化氢(H2S)对低氧大鼠肺动脉胶原重构的调节机制。方法 Wistar大鼠随机分为对照组、低氧组、低氧 NaHS组各6只。采用比色法测定血浆H2S含量,免疫组织化学方法检测肺动脉Ⅰ型胶原表达,原位分子杂交方法检测肺动脉金属蛋白酶组织抑制因子-1(TIMP-1)mRNA表达。结果 与低氧组比较,低氧 NaHS组大鼠血浆H2S含量显著增高,肺动脉Ⅰ型胶原及TIMP-1 mRNA表达均明显下调。血浆H2S含量与肺动脉TIMP-1 nRNA表达呈明显负相关。结论 H2S可能通过减少TIMP-1合成从而增加低氧大鼠中、小型肺动脉的胶原降解,进而改善低氧大鼠肺动脉胶原重构。

Impact of hydrogen sulfide on tissue inhibitor of metalloproteinase- 1 gene expression in pulmonary arteries of rats under hypoxia

Objective To explore the mechanisms by which hydrogen sulfide (H2S) regulates collagen metabolism during hypoxic pulmonary vascular structural remodeling. Methods Wistar rats were randomly divided into control group (n=6), hypoxia group (n = 6) and hypoxia NaHS group(n= 6) H2S content in plasma was measured with spectrophotometry. The expression of collagen I was detected by immunohistochemistry. The expression of tissue inhibitor of metalloproteinase-1(TIMP-1) mRNA was detected with situ hybridization Results Compared with hypoxia group, H2S content in plasma increased significantly and the expressions of collagen I and TIMP-1 mRNA in pulmonary arteries were down- regulated in hypoxia NaHS group. The H2S content in plasma negatively correlated with TIMP-I mRNA expression. Conclusions H2S increases the degradation of collagen in small and media pulmonary arteries of rats under hypoxia by decreasing the synthesis of TIMP-1, and therefore, attenuats the collagen remodeling in pulmonary arteries of hypoxic rats.