Sodium hydrosulfide alleviated pulmonary vascular structural remodeling induced by high pulmonary bl

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:chenzhipengo
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Aim:To explore the possible role of endogenous hydrogen sulfide (H_2S),a novelgasotransmitter,in the pathogenesis of pulmonary vascular structural remodeling(PVSR) induced by high pulmonary blood flow.Methods:Thirty-two Sprague-Dawley male rats were randomly divided into sham,shunt,sham+NaHS (a H_2Sdonor) and shunt+NaHS groups.Rats in shunt and shunt+NaHS groups under-went an abdominal aorta-inferior vena cava shunt,and rats in shunt+NaHS andsham+NaHS groups were intraperitoneally injected with NaHS.PVSR was inves-tigated using optical microscope and transmission electron microscope.Lungtissue H_2S was evaluated by sulfide-sensitive electrodes.Nitric oxide synthase(NOS),heme oxygenase (HO-1),proliferative cell nuclear antigen (PCNA) andextracellular signal-regulated kinase (ERK) activation were analyzed by Westernblotting.Results:After 11 weeks of shunting,PVSR developed with a decrease inlung tissue H_2S production and an increase in nitric oxide (NO).However,lungtissue carbon monoxide (CO) did not change.After the treatment with NaHS for11 weeks,H_2S donor ameliorated PVSR and downregulated PCNA expression andERK activation with an increase in lung tissue CO production and HO-1 proteinexpression but a decrease in NO production,NOS activity and eNOS proteinexpression in shunted rats.Conclusions:H_2S exerted a regulatory effect on PVSRinduced by high pulmonary blood flow.Meanwhile,H_2S down-regulated theERK/MAPK signal pathway,inhibited the NO/NOS pathway and enhanced theCO/HO pathway in rats with high pulmonary blood flow. Aim: To explore the possible role of endogenous hydrogen sulfide (H_2S), a novel gastrransmitter, in the pathogenesis of pulmonary vascular structural remodeling (PVSR) induced by high pulmonary blood flow. Methods: Thirty-two Sprague-Dawley male rats were randomly divided into sham, shunt, sham + NaHS (a H_2Sdonor) and shunt + NaHS groups. Rats in shunt and shunt + NaHS groups under-went an abdominal aorta-ana vena cava shunt, and rats in shunt + NaHS andsham + NaHS groups were intraperitoneally injected with NaHS.PVSR was in-tated using an optical microscope and transmission electron microscope. Lung Tissue H_2S was evaluated by sulfide-sensitive electrodes. Nitric oxide synthase (NOS), heme oxygenase (HO-1), proliferative cell nuclear antigen (PCNA) Results: After 11 weeks of shunting, PVSR developed with a decrease in human tissue H 2 S production and an increase in nitric oxide (NO) .However, lungtissue carbon monoxid After the treatment with NaHS for 11 weeks, H 2 S donor ameliorated PVSR and downregulated PCNA expression and ERK activation with an increase in lung tissue CO production and HO-1 proteinexpression but a decrease in NO production, NOS activity and eNOS proteinexpression in shunted rats. Conclusions: H 2 S exerted a regulatory effect on PVS Induced by high pulmonary blood flow. Meanwhile, H 2 S 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.
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