中国药理学通报2024，Vol.40Issue(8)：1454-1461,8.DOI:10.12360/CPB202312060
RASAL1在同型半胱氨酸致肺血管内皮通透性增加中的作用及机制研究
Role and mechanism of RASAL1 in increase of pulmonary vascular endothelial permeability induced by homocysteine
摘要
Abstract
Aim To investigate the effect of homocys-teine(Hcy)on the permeability of pulmonary micro-vascular endothelial cells(PMVECs)and the role and mechanism of RASAL1.Methods CBS+/-mice were fed a high methionine diet(HMD)for 16 weeks to replicate an animal model of hyperhomocysteinemia(HHcy).HE staining was used to observe the changes in lung tissue structure.qRT-PCR was used to detect the levels of RASAL1 and DNMT1 mRNA in lung tis-sue.Western blot was used to detect the expression of RASAL1,DNMT1,ZO-1,and VE cadherin proteins.Methylation specific PCR was used to detect methyla-tion in the RASAL1 promoter region.PMVECs were transfected with Ad-RASAL1 to detect the expression of ZO-1 and VE cadherin.The si-DNMT1 interference fragment was transfected into PMVECs,and the ex-pression of the RASAL1 was detected by qRT-PCR and Western blot.Results Serum Hcy level of HMD mice was significantly raised,and HE staining showed severe structural disorder in lung tissue.The expres-sion of RASAL1,ZO-1,and VE cadherin was de-creased,while the expression of DNMT1 was in-creased.The degree of methylation in the RASAL1 promoter region was raised.The expression of ZO-1 and VE cadherin increased after PMVECs were trans-fected with Ad-RASAL1.After knocking down DN-MT1,RASAL1 expression was increased.Conclusion Hcy can increase the permeability of PMVECs,and its mechanism is related to the upregulation of RASAL1 methylation level.关键词
同型半胱氨酸/RASAL1/肺微血管内皮细胞/通透性/DNA甲基化/DNMT1Key words
homocysteine/RASAL1/pulmonary mi-crovascular endothelial cells/permeability/DNA methylation/DNMT1分类
医药卫生引用本文复制引用
李昕怡,秦凯悦,杨梓尧,张玲,李珍,杨亚丽,徐茜,杨晓玲..RASAL1在同型半胱氨酸致肺血管内皮通透性增加中的作用及机制研究[J].中国药理学通报,2024,40(8):1454-1461,8.基金项目
国家自然基金资助项目(No 81960063) （No 81960063）
宁夏自然基金资助项目(No 2021AAC2012) （No 2021AAC2012）
