Sodium hydrosulfide alleviated pulmonary vascular structural remodeling induced by high pulmonary blood flow in rats  

作　　者：Xiao-hui LI Jun-bao DU Ding-fang BU Xiu-ying TANG Chao-shu TANG 

机构地区：[1]Department of Pediatrics, Peking University First Hospital, Key Laboratory of Molecular Cardiovascular Diseases, Ministry of Education [2]Laboratory Center [3]Laboratory of Electron Microscopy, Peking University First Hospital, Beijing 100034, China [4]Department of Physiology,Peking University Health Science Center, Beijing 100083, China

出　　处：《Acta Pharmacologica Sinica》2006年第8期971-980,共10页中国药理学报（英文版）

基　　金：Project supported by the National Science Fund for Distinguished Young Scholars(№ 30425010);the State Major Basic Research Project of China;the Natural Science Foundation of Beijing,China(№ 7052043).

摘　　要：Aim： To explore the possible role of endogenous hydrogen sulfide （H2S）, a novel gasotransmitter, in the pathogenesis of pulmonary vascular structural remodeling （PVSR） induced by high pulmonary blood flow. Methods： Thirty-two SpragueDawley male rats were randomly divided into sham, shunt, sham＋NaHS （a H2S donor） and shunt＋NaHS groups. Rats in shunt and shunt＋NaHS groups underwent an abdominal aorta-inferior vena cava shunt, and rats in shunt＋NaHS and sham＋NaHS groups were intraperitoneally injected with NaHS. PVSR was investigated using optical microscope and transmission electron microscope. Lung tissue H2S was evaluated by sulfide-sensitive electrodes. Nitric oxide synthase （NOS）, heme oxygenase （HO- 1）, proliferative cell nuclear antigen （PCNA） and extracellular signal-regulated kinase （ERK） activation were analyzed by Western blotting. Results： After 11 weeks of shunting, PVSR developed with a decrease in lung tissue H2S production and an increase in nitric oxide （NO）. However, lung tissue carbon monoxide （CO） did not change. After the treatment with NaHS for 11 weeks, H2S donor ameliorated PVSR and downregulated PCNA expression and ERK activation with an increase in lung tissue CO production and HO-1 protein expression but a decrease in NO production, NOS activity and eNOS protein expression in shunted rats. Conclusions： H2S exerted a regulatory effect on PVSR induced by high pulmonary blood flow. Meanwhile, H2S down-regulated the ERK/MAPK signal pathway, inhibited the NO/NOS pathway and enhanced the CO/HO pathway in rats with high pulmonary blood flow.Aim： To explore the possible role of endogenous hydrogen sulfide （H2S）, a novel gasotransmitter, in the pathogenesis of pulmonary vascular structural remodeling （PVSR） induced by high pulmonary blood flow. Methods： Thirty-two SpragueDawley male rats were randomly divided into sham, shunt, sham＋NaHS （a H2S donor） and shunt＋NaHS groups. Rats in shunt and shunt＋NaHS groups underwent an abdominal aorta-inferior vena cava shunt, and rats in shunt＋NaHS and sham＋NaHS groups were intraperitoneally injected with NaHS. PVSR was investigated using optical microscope and transmission electron microscope. Lung tissue H2S was evaluated by sulfide-sensitive electrodes. Nitric oxide synthase （NOS）, heme oxygenase （HO- 1）, proliferative cell nuclear antigen （PCNA） and extracellular signal-regulated kinase （ERK） activation were analyzed by Western blotting. Results： After 11 weeks of shunting, PVSR developed with a decrease in lung tissue H2S production and an increase in nitric oxide （NO）. However, lung tissue carbon monoxide （CO） did not change. After the treatment with NaHS for 11 weeks, H2S donor ameliorated PVSR and downregulated PCNA expression and ERK activation with an increase in lung tissue CO production and HO-1 protein expression but a decrease in NO production, NOS activity and eNOS protein expression in shunted rats. Conclusions： H2S exerted a regulatory effect on PVSR induced by high pulmonary blood flow. Meanwhile, H2S down-regulated the ERK/MAPK signal pathway, inhibited the NO/NOS pathway and enhanced the CO/HO pathway in rats with high pulmonary blood flow.

关 键 词：hydrogen sulfide pulmonary hypertension structure remodeling nitric oxide/nitricoxide synthase carbon monoxide/heme oxygenase 

分 类 号：R544.1[医药卫生—心血管疾病]