Experimental Study of CYP2J2 Improving Cardiovascular Injury after Chronic Intermittent Hypoxia by Activating Notch1 Pathway
HE Danna
ZHAO Ruiping
LI Wei
YANG Yang
LU Yaojun
Abstract：Objective:To investigate the effect of cytochrome P450 epoxygenase 2J2(CYP2J2)on cardiovascular injury in chronic intermittent hypoxia(CIH)model rats.Methods:Fifty SD rats were randomly divided into control group,CYP2J2 group,CIH group,CIH+CYP2J2 group and CIH+CYP2J2+DAPT group,with 10 rats in each group.CIH model was established in CIH group,CIH+CYP2J2 group,and CIH+CYP2J2+DAPT group.After successful modeling,rats in CYP2J2 group,CIH+CYP2J2 group,and CIH+CYP2J2+DAPT group were injected with recombinant adenovirus carrying CYP2J2 gene in a one-time tail vein.In CIH+CYP2J2+DAPT group,DAPT was injected intraperitoneally.After 2 weeks,left ventricular shortening fraction(FS),ejection fraction(EF),left ventricular end-systolic volume(LVESV),and left ventricular end-diastolic volume(LVEDV)were measured by high-resolution small animal ultrasound imaging system.Serum creatine kinase isoenzyme(CK-MB)and cardiac troponin I(cTnI)were detected by automatic biochemical analyzer.Nitric oxide(NO)in serum was determined by nitrate reductase method.Plasma endothelin-1(ET-1)was detected by enzyme-linked immunosorbent assay(ELISA).Hematoxylin-eosin(HE)staining was used to observe the morphological changes of aorta and myocardium.The apoptosis of cardiomyocytes was observed by dUTP notch end labeling(TUNEL)staining.The activity of superoxide dismutase(SOD)and the content of malondialdehyde(MDA)in myocardial tissue were detected by the biochemical index detection kit.Notch receptor 1(Notch1)signaling pathway related protein expression was detected by Western Blot.Results:Compared with the CIH group,FS and NO levels in the CIH+CYP2J2 group increased,LVESV,LVEDV,CK-MB,cTnI,ET-1 levels decreased,the aorta structure was clear,cell swelling,shedding,vascular wall thickening and other phenomena were improved,myocardial fiber breakage,myocardial cell swelling and other phenomena reduced,while the proportion of TUNEL positive cells decreased,SOD activity increased,MDA content decreased,and the relative expressions of Notch1 and Hes1 proteins decreased in myocardial tissue,with statistical significance(P＜0.05).Compared with the CIH+CYP2J2+DAPT group,FS and NO levels in the CIH+CYP2J2+DAPT group decreased,LVESV,LVEDV,CK-MB,cTnI,ET-1 levels increased,aortic and myocardial tissue pathological damage was significant,and the proportion of TUNEL positive cells in myocardial tissue significantly increased,while SOD activity decreased,MDA content increased,and the relative expression levels of Notch1 and Hes1 proteins down-regulated,with statistical significance(P＜0.05).Conclusion:CYP2J2 could improve cardiovascular injury,reduce cardiomyocyte apoptosis,and inhibit oxidative stress in CIH rats,which might be related to the activation of Notch1 pathway.
Keywords：chronic intermittent hypoxiacytochrome P450 epoxygenase 2J2cardiovascular injurycardiomyocyte apoptosisNotch receptor 1 pathwayratsexperimental study
Publication Date：2025-01-31
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：8( 215-222 )