Increased ENOS Expression Inhibits ICAM-1 And Alleviates Vascular Adhesion In The Aorta Of Septic Mice

Objective: To investigate the effect of nitric oxide synthase(eNOS)expression on intermolecular cell adhesion molecule-1(ICAM-1)in thoracic aorta during sepsis and to explore its potential mechanism.Methods: C57 male mice(6-8 weeks old)were subjected to cecal ligation and puncture(CLP)to establish sepsis model.The mice were randomly divided into four groups: 1、control group 2、control +L-NAME group(L-NAME,NOS inhibitor)3、CLP group 4、CLP +L-NAME group.(n ≥ 4),12 hours or 24 hours later,the aorta of each group was collected for immunohistochemistry,immunofluorescence,myeloperoxidase(MPO)staining and Western blot detection,and RT-qPCR was used to detect the m RNA levels of eNOS and ICAM-1.Bovine aortic endothelial cells(BAECs)were isolated and cultured and treated with concentration gradient and time gradient lipopolysaccharide(lipopolysaccharide,LPS)to detect the expression of eNOS and ICAM-1;BAECs pretreated with L-NAME(1m M)was stimulated with appropriate concentration of LPS and detected by Western blot and RT-qPCR;and the release level of NO in cell culture medium was detected.Results:(1)At 24 h after CLP,the expression of eNOS in mesentery decreased,while the expression of eNOS in aorta increased.At the same time,the expression of eNOS and ICAM-1 was time-dependent.(2)Administration of L-NAME(100mg/kg)before CLP operation could significantly increase the expression of ICAM-1 induced by CLP,but there was no significant change in the protein expression induced by direct injection of L-NAME,which was further confirmed by immunohistochemistry,immunofluorescence and MPO staining.(3)In vitro experiment,it was found that LPS increased the level of eNOS in a short time(within 4 h),and the expression of ICAM-1 was time-dependent.After(4)L-NAME inhibited the activity of eNOS,the expression level of ICAM-1increased significantly.Conclusion: The expression of eNOS and ICAM-1 in aorta increased in a time-dependent manner during sepsis.The increase of eNOS content could inhibit the expression of ICAM-1,which may be involved in improving vascular adhesion.