Nrf2 Regulation by Sulforaphane to Prevent Right Ventricular Injury and Pulmonary Vascular Remodeling in Rats with Pulmonary Arterial Hypertension
Objective:To explore the mechanism of sulforaphane prevent right ventricular injury and reduce pulmonary vascular remodeling in rats with pulmonary arterial hypertension(PAH)by regulating transcription factor nuclear factor erythrocyte 2-associated factor 2(Nrf2).Methods:Thirty adult male SD rats were randomly divided into control group,model group and sulforaphane group,with 10 rats in each group.The rat model of pulmonary arterial hypertension was established in model group and sulforaphane group.Right ventricular heart index(CI),pulmonic velocity-time integral(VTI),pulmonic acceleration time(PAT),pulmonic ejection time(PET),right ventricular diastolic inner diameter(IDd),right ventricular free wall thickness(FW),and right ventricular isovolute relaxation time(IVRT)were measured,tricuspid valve early diastolic myocardial contraction(RVE),tricuspid valve early diastolic myocardial diastolic velocity(RVE'),systolic blood pressure velocity(S')and myocardial performance(Tei)by using a high-frequency,high-resolution digital imaging platform.The expression of Nrf2 and NQO1 proteins in rats were detected by Western Blot.Real-time polymerase chain reaction(RT-PCR)was used to detect the mRNA expression of fibronectin(FN),connective tissue growth factor(CTGF),collagen-type Ⅰ α1(COL1A1),collagen-type Ⅰ α2(COL1A2),tumor necrosis factor α(TNF-α),interleukin-1β,and IL-6 mRNA expression.Oxidative stress markers malondialdehyde(MDA),glutathione(GSH),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and total antioxidant capacity(TAC)were tested.The whole lung α-SMA protein expression was analyzed by immunohistochemistry.Results:The levels of SOD,GSH-Px,TAC,and GSH,CI,VTI,PAT,PET,RVE',S',Tei index,Nrf2,α-SMA,and NQO1 in model group were lower than those in the control group(P<0.05).SOD,GSH-Px,TAC,GSH levels,CI,pulmonary valve VTI,PAT/PET,RVE',S',Tei index,Nrf2,α-SMA,and NQO1 expression in sulforaphane group were higher than those in the model group(P<0.05).IDd,FW,IVRT,RVE/RVE',FN,CTGF,COL1A1,COL1A2,TNF-α,IL-1β,and IL-6 mRNA protein expression and MDA levels in model group were more than those in the control group(P<0.05).The expression of IDd,FW,IVRT,RVE/RVE',FN,CTGF,COL1A1,COL1A2,TNF-α,IL-1β,and IL-6 mRNA,α-SMA protein,and MDA levels in sulforaphane group were mower than those in the model group(P<0.05).Conclusion:Sulforaphane reduces pulmonary vascular remodeling in hypoxic expose-induced PAH and improves right ventricular dysfunction by uspregulating Nrf2/NQO1.Sulforaphane may be useful as a novel adjuvant therapy for the prevention of PAH.
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