中山大学学报（医学科学版）2025，Vol.46Issue(1)：70-80,11.
NAD+激活SIRT3/IDH2信号通路改善高血压血管内皮功能障碍
NAD+Ameliorates Endothelial Dysfunction in Hypertension via Activation of SIRT3/IDH2 Signal Pathway
摘要
Abstract
[Objective]To investigate the effect of nicotinamide adenine dinucleotide on vascular endothelial injury in hypertension and its molecular mechanism.[Methods]C57BL/6J mice were randomly divided into saline group(Saline)and hypertension group(Ang Ⅱ,which were infused with Ang Ⅱ via subcutaneously implanted osmotic pumps),and supplemented daily with nicotinamide mononucleotide(300 mg/kg),a precursor of NAD+.Blood pressure,endothelial relaxation function and pulse wave velocity were measured after 4 weeks.Wound healing assay and adhesion assay were used to evaluate the function of endothelial cells in vitro.mtROS levels were detected by immunofluorescence staining.RT-PCR was used to detect the mRNA expression of mtDNA,SIRT3 and isocitrate dehydrogenase 2(IDH2).8-hydroxy-2'-deoxyguanosine levels were detected by enzyme-linked immunosorbent assay.The protein expression levels of p-eNOS,eNOS,SIRT3 and IDH2 were detected by Western blot.[Results]NMN supplementation reduced blood pressure(P<0.001)and improved endothelial function and arterial stiffness(P<0.001)in hypertensive mice.In vitro,NMN improved endothelial function in Ang Ⅱ-stimulated endothelial cells(P<0.05)and attenuated mitochondrial oxidative stress levels(P<0.001).Mechanistically,NMN elevated SIRT3 activity(P<0.001),which subsequently enhanced IDH activity(P<0.001)and reduced oxidative stress levels in endothelial cells.Conversely,knockdown of IDH2 would reverse the effect of SIRT3 in improving endothelial function(P<0.001).[Conclusion]NAD+lowers blood pressure and enhances vascular function in hypertension by reducing the level of oxidative stress in endothelial cells through activation of the SIRT3/IDH2 signal pathway.关键词
高血压/血管内皮损伤/烟酰胺腺嘌呤二核苷酸/SIRT3/氧化应激Key words
hypertension/vascular endothelial injury/nicotinamide adenine dinucleotide/SIRT3/oxidative stress分类
临床医学引用本文复制引用
丘雨旻,陈曦,张建宁,刘张弛,朱秋霞,张美信,陶军,吴杏..NAD+激活SIRT3/IDH2信号通路改善高血压血管内皮功能障碍[J].中山大学学报（医学科学版）,2025,46(1):70-80,11.基金项目
国家自然科学基金(823B2009 （）
82270460) （）
广东省基础与应用研究基金(2021A1515220019) （2021A1515220019）
博士后基金(GZB20240899) （GZB20240899）
广州市重点研发计划(202206080004) （202206080004）
