Li Xiaohui, Du Junbao, Jin Hongfang, Geng Bin, Tang Chaoshu
Department of Pediatrics, Peking University First Hospital and Key Laboratory of Molecular Cardiology, Ministry of Education, Xi-An Men Street No. 1, West District, Beijing, 100034, P.R. China.
Heart Vessels. 2008 Nov;23(6):409-19. doi: 10.1007/s00380-008-1059-4. Epub 2008 Nov 27.
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 H(2)S 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 H(2)S is involved in the development of pulmonary artery collagen remodeling induced by high pulmonary blood flow.
本研究旨在探讨氢硫化钠（NaHS）对高肺血流量大鼠肺动脉胶原重塑的影响。将32只Sprague-Dawley大鼠随机分为假手术组、分流组、假手术+NaHS（一种H2S供体）组和分流+NaHS组。分流11周后，检测平均肺动脉压（MPAP）、肺动脉相对中膜面积（RMA）、肺组织中H2S浓度、血浆内皮素-1（ET-1）水平以及肺组织中ET-1 mRNA水平。通过免疫组织化学法评估Ⅰ型和Ⅲ型胶原。进行羟脯氨酸测定和天狼星红染色。通过免疫组织化学法评估基质金属蛋白酶-13（MMP-13）、金属蛋白酶组织抑制剂-1（TIMP-1）和结缔组织生长因子（CTGF）。分流11周后，大鼠出现明显的肺动脉高压和肺动脉胶原重塑，同时肺组织H2S含量降低。NaHS治疗11周后，肺组织H2S含量增加，而MPAP降低，RMA减小。同时，腺泡内肺动脉Ⅰ型和Ⅲ型胶原蛋白表达受到抑制，但MMP-13/TIMP-1比值升高，血浆ET-1含量、肺组织ET-1 mRNA和CTGF表达降低。H2S下调参与了高肺血流量诱导的肺动脉胶原重塑的发生发展。
