Objective To explore the role and mechanism of Notch1 pathway in regulating CD4+CD25+Foxp3+regulatory T cells(Treg)in renal vascular hypertension(RVH).Methods Two hundred and twenty patients treated in the Department of Nephrology of Sichuan Provincial People's Hospital from January 2019 to January 2022 were enrolled as RVH group,and 220 patients with essential hypertension(EH)in the same period were selected as EH group;another 220 healthy examinees were selected as control group(NC).After propensity score matching,ten cases were included in each group.Flow cytometry was used to determine the proportion of CD4+CD25+Foxp3+Treg,interleukin-10(IL-10),transforming growth factor-β(TGF-β),and Ki-67 levels in peripheral blood mononu-clear cell(PBMC).Real-time quantitative polymerase chain reaction(PCR)was employed to measure the messenger RNA levels of Notch1,DLL,DLL4,Jagged1,and Jagged4.Western blot analysis was conducted to determine the protein levels of Notch1,hes family bHLH transcription factor(Hes)1,and Hes5.Results Flow cytometry re-sults showed that compared with NC group,RVH group had significantly lower proportion of CD4+CD25+Foxp3+Treg cells,TGF-β and Ki-67 expression levels,and higher IL-10 expression level,with significant differences(P＜0.001).Compared with RVH group,EH group had significantly higher proportion of CD4+CD25+Foxp3+Treg cells,TGF-β and Ki-67 expression levels,and lower IL-10 expression level,with significant differences(P＜0.001).Real-time quantitative PCR results showed that RVH group also had significantly higher relative expression levels of Notch receptor Notch1 mRNA,Notch ligand δ-like ligand(DLL)1,DLL4,Jagged1 and Jagged2 mRNA in PBMC than NC group and EH group,with significant differences(P＜0.001).Western blot results showed that af-ter adding Notch1 signaling pathway inhibitor,Hes1 and Hes5 expression in peripheral CD4+CD25+Foxp3+Treg cells of patients decreased significantly(P＜0.001),while CD4+CD25+Foxp3+Treg proportion and TGF-β expres-sion level increased significantly(P＜0.001).Conclusion Notch1 signaling pathway plays an immunoregulatory role in RVH regulated by CD4+CD25+Foxp3+Treg cells.Regulation of Notch1 signaling pathway can significantly promote the proliferation of CD4+CD25+Foxp3+Treg cells and the ability to secrete anti-inflammatory factors.
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