中国药房2024，Vol.35Issue(2)：179-185,7.DOI:10.6039/j.issn.1001-0408.2024.02.10
GW501516对低氧致肺动脉内皮细胞损伤的影响及机制
Effects of GW501516 on the injury of pulmonary artery endothelial cells induced by hypoxia and its mechanism
摘要
Abstract
OBJECTIVE To investigate the effects of the peroxisome proliferator-activated receptors δ(PPARδ)agonist GW501516 on the injury of pulmonary artery endothelial cells(PAECs)induced by hypoxia and its mechanism.METHODS The cytotoxic effects of GW501516 were observed by detecting the relative survival rate of PAECs;the protein expression of PPARδ was determined by Western blot assay.The cellular model of PAECs injury was established under hypoxic conditions;using antioxidant N-acetylcysteine(NAC)as positive control,the effects of GW501516 on cell injury and reactive oxygen species(ROS)production were investigated by detecting cell apoptotic rate,cell viability,lactate dehydrogenase(LDH)activity and ROS levels.Using nuclear factor erythroid 2-related factor 2(Nrf2)activator dimethyl fumarate(DMF)as positive control,PAECs were incubated with GW501516 and/or Nrf2 inhibitor ML385 under hypoxic conditions;the mechanism of GW501516 on PAECs injury induced by hypoxia was investigated by detecting cell injury(cell apoptosis,cell viability,LDH activity),the levels of superoxide dismutase(SOD),glutathione peroxidase(GPx),catalase(CAT),malondialdehyde(MDA)and ROS,the expressions of Nrf2,heme oxygenase-1(HO-1)and cleaved-caspase-3(C-caspase-3)protein.RESULTS The results demonstrated that hypoxia inhibited the protein expression of PPARδ(P＜0.05),while GW501516 promoted the protein expression of PPARδ in hypoxia-exposed PAECs without obvious cytotoxic effects.GW501516 inhibited the apoptosis of PAECs,improved cell viability,and reduced LDH activity and ROS levels.GW501516 could up-regulate the protein expression of HO-1 in PAECs and the levels of SOD,GPx and CAT,while down-regulated the levels of MDA and ROS by activating the Nrf2 pathway(P＜0.05);but Nrf2 inhibitor ML385 could reverse the above effects of GW501516(P＜0.05).GW501516 exerted similar effects to Nrf2 activator DMF in down-regulating the expression of C-caspase-3 and inhibiting the injury of PAECs under conditions of hypoxia(P＜0.05).Moreover,Nrf2 inhibitor ML385 reversed the inhibition effects of GW501516 on PAECs injury(P＜0.05).CONCLUSIONS GW501516 can relieve the hypoxia-induced injury of PAECs via the inhibition of oxidative stress,the mechanism of which may be associated with activating Nrf2.关键词
GW501516/低氧/肺动脉内皮细胞/氧化应激/损伤/核因子E2相关因子2Key words
GW501516/hypoxia/pulmonary artery endothelial cells/oxidative stress/injury/nuclear factor erythroid 2-related factor 2分类
医药卫生引用本文复制引用
陈昌贵,易春峰,余志华,王栋,李立为,贺立群..GW501516对低氧致肺动脉内皮细胞损伤的影响及机制[J].中国药房,2024,35(2):179-185,7.基金项目
湖北省自然科学基金项目(No.2019CFB405) （No.2019CFB405）
