Sodium hydrosulfide alleviates pulmonary artery collagen remodeling in rats with high pulmonary blood flow
Sodium hydrosulfide alleviates pulmonary artery collagen remodeling in rats with high pulmonary blood flow
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硫氢化钠减轻高肺血流大鼠肺动脉胶原重塑
DOI：
10.1007/s00380-008-1059-4
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发表时间：
2008-11-01
影响因子：
1.5
通讯作者：
Tang Chaoshu
中科院分区：
文献类型：
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作者：
Li Xiaohui;Du Junbao;Tang Chaoshu
本研究旨在探讨硫氢化钠（NaHS）对高肺血流大鼠肺动脉胶原重构的影响。将32只SD大鼠随机分为假手术组、分流组、假手术+ NaHS（H2S供体）组和分流+ NaHS组。术后11周检测肺动脉平均压（MPAP）、肺动脉相对中位面积（RMA）、肺组织硫化氢（H2S）浓度、血浆内皮素-1（ET-1）水平及肺组织ET-1 mRNA表达。通过免疫组织化学方法评价I型胶原和III型胶原。进行羟脯氨酸测定和琥珀红染色。免疫组化检测基质金属蛋白酶-13（MMP-13）、金属蛋白酶组织抑制因子-1（TIMP-1）和结缔组织生长因子（CTGF）。分流11周后，大鼠表现出显著的肺动脉高压和肺动脉胶原重塑，并伴有肺组织H2S含量降低。NaHS处理11周后，肺组织H2S含量增加，MPAP减弱，RMA减少。肺动脉I型胶原和III型胶原蛋白表达受到抑制，MMP-13/TIMP-1比值升高，血浆ET-1含量和肺组织ET-1 mRNA及CTGF表达下降。H2S的下调参与了高肺血流量诱导的肺动脉胶原重塑的发展。
This study aimed to explore the effect of sodium hydrosulfide (NaHS) on pulmonary artery collagen remodeling in rats with high pulmonary blood flow. Thirty-two Sprague-Dawley rats were randomly divided into a sham group, shunt group, sham + NaHS (an H2S donor) group, and shunt + NaHS group. After 11 weeks of shunting, mean pulmonary artery pressure (MPAP), relative median area (RMA) of pulmonary arteries, H2S concentration in lung tissues, plasma endothelin-1 (ET-1) levels, and ET-1 mRNA in lung tissues were investigated. Collagen I and collagen III were evaluated by immunohistochemistry. Hydroxyproline assay and Sirius-red staining were performed. Matrix metalloproteinase-13 (MMP-13), tissue inhibitor of metalloproteinase-1 (TIMP-1), and connective tissue growth factor (CTGF) were evaluated by immunohistochemistry. After 11 weeks of shunting, rats showed a significant pulmonary hypertension and pulmonary artery collagen remodeling in association with a decrease in lung tissue H2S content. After NaHS treatment for 11 weeks, lung tissue H2S content was increased, whereas MPAP was attenuated and RMA was reduced. Meanwhile, pulmonary artery collagen I and collagen III protein expressions of intra-acinar pulmonary arteries were inhibited, but MMP-13/TIMP-1 ratio was augmented with a decreased plasma ET-1 content and lung tissue ET-1mRNA and CTGF expressions. The downregulation of H2S is involved in the development of pulmonary artery collagen remodeling induced by high pulmonary blood flow.