Mechanism of rosuvastatin attenuating high glucose-induced vascular en-dothelial injury based on bioinformatics
10.3969/j.issn.1000-4718.2024.12.005
- VernacularTitle:基于生物信息学探讨瑞舒伐他汀减轻高糖所致血管内皮损伤的机制
- Author:
Shiqing JIANG
1
;
Jiaxin CHEN
;
Yujia WANG
;
Xiaohui LIN
;
Yongfang LEI
Author Information
1. 宁德师范学院附属宁德市医院,福建 宁德 352000
- Publication Type:Journal Article
- Keywords:
bioinformatics;
diabetes mellitus;
human umbilical vein endothelial cells;
rosuvastatin
- From:
Chinese Journal of Pathophysiology
2024;40(12):2226-2237
- CountryChina
- Language:Chinese
-
Abstract:
AIM:This study investigated the protective effects and underlying mechanisms of rosuvastatin(RST)in mitigating high glucose(HG)-induced damage in human umbilical vein endothelial cells(HUVECs),comple-mented by bioinformatics analysis.METHODS:Network pharmacology was employed to identify the potential targets and signaling pathways of RST in treating HG-induced vascular endothelial dysfunction.Molecular docking techniques were used to evaluate the binding affinity of RST to these core targets.The HUVECs were cultured in vitro and assigned into control,HG,and HG+RST(0.01,0.1,1,2,5 and 10 μmol/L)groups.Cell viability was determined using the MTS as-say.Levels of lactate dehydrogenase(LDH)and nitric oxide(NO)were quantified using chemical colorimetric assays.The mRNA levels of endothelial nitric oxide synthase(eNOS),claudin-1(CLDN-1),occludin(OCLN),zonula oc-cludens-1(ZO-1),aldose reductase(AR),Janus kinase 2(JAK2),mitogen-activated protein kinase 1(MAPK1),Ras homologous gene family member A(RHOA)and heat shock proteins 90AB1(HSP90AB1)were assessed by RT-qPCR.Western blot analysis was used to evaluate protein levels of eNOS,OCLN and ZO-1.RESULTS:Network pharmacology analysis suggested that RST may improve HG-induced vascular endothelial dysfunction by influencing the chemokine sig-naling pathway,tyrosine metabolism,MAPK signaling pathway,and hypoxia-inducible factor 1 alpha signaling pathway.The MTS assay indicated that RST significantly enhanced cell viability in an HG environment(P＜0.01)and reduced HG-induced damage in HUVECs.Compared with the control group,the HG group showed a significant increase in LDH levels(P＜0.01)and decreases in NO,eNOS,CLDN-1,OCLN and ZO-1 levels(P＜0.05).Additionally,the mRNA levels of AR,JAK2,MAPK1 and RHOA were elevated(P＜0.01),and HSP90AB1 was reduced in the HG group(P＜0.05).Rel-ative to the HG group,RST treatment significantly decreased LDH levels(P＜0.01)and increased the levels of NO,eNOS,CLDN-1,OCLN and ZO-1(P＜0.01).Moreover,the mRNA levels of AR,JAK2,MAPK1 and RHOA were re-duced(P＜0.01),and HSP90AB1 expression was increased in the HG+RST group(P＜0.01).CONCLUSION:RST ef-fectively attenuates HG-induced endothelial injury.This protective effect is potentially mediated by downregulating AR,JAK2,MAPK1,and RHOA expression and upregulating HSP90AB1 expression.
