NAD+激活SIRT3/IDH2信号通路改善高血压血管内皮功能障碍
R544.1; [目的]探讨烟酰胺腺嘌呤二核苷酸在改善高血压血管内皮损伤中的作用及其分子机制.[方法]利用渗透泵构建高血压小鼠模型,将C57BL/6J小鼠随机分为生理盐水组(Saline)和高血压组(Ang Ⅱ),每天补充NAD+前体——烟酰胺单核苷酸(300 mg/kg),4周后检测小鼠血压、内皮舒张功能、脉搏波传导速度.采用迁移实验和划痕实验评估体外内皮细胞功能;采用免疫荧光染色法检测mtROS水平;采用RT-PCR检测mtDNA、SIRT3、异柠檬酸脱氢酶2(IDH2)的mRNA表达;采用酶联免疫吸附法检测8-羟基-2'-脱氧鸟苷的水平;采用Western blot法检测p-e...
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| Published in | Zhongshan da xue xue bao. Zhongshan daxue xuebao yixue kexue ban = Journal of Sun Yat-sen University. Yi xue ke xue ban Vol. 46; no. 1; pp. 70 - 80 |
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| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | Chinese |
| Published |
中山大学附属第一医院高血压血管病科,广东 广州 510080
2025
Editorial Office of Journal of Sun Yat-sen University |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1672-3554 |
| DOI | 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).20241122.001 |
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| Abstract | R544.1; [目的]探讨烟酰胺腺嘌呤二核苷酸在改善高血压血管内皮损伤中的作用及其分子机制.[方法]利用渗透泵构建高血压小鼠模型,将C57BL/6J小鼠随机分为生理盐水组(Saline)和高血压组(Ang Ⅱ),每天补充NAD+前体——烟酰胺单核苷酸(300 mg/kg),4周后检测小鼠血压、内皮舒张功能、脉搏波传导速度.采用迁移实验和划痕实验评估体外内皮细胞功能;采用免疫荧光染色法检测mtROS水平;采用RT-PCR检测mtDNA、SIRT3、异柠檬酸脱氢酶2(IDH2)的mRNA表达;采用酶联免疫吸附法检测8-羟基-2'-脱氧鸟苷的水平;采用Western blot法检测p-eNOS、eNOS、SIRT3、IDH2蛋白表达水平.[结果]补充NMN降低了高血压小鼠血压(P<0.001),改善内皮功能和动脉僵硬度(P<0.001);体外实验中,NMN可改善Ang Ⅱ刺激所致的内皮细胞舒张功能下降(P<0.05)和减轻线粒体氧化应激水平(P<0.001).机制上,NMN提升了SIRT3活性(P<0.001),进而增强了IDH的活性(P<0.001),从而改善内皮细胞氧化应激水平;相反,敲低IDH2后将减弱SIRT3改善内皮功能的作用(P<0.001).[结论]NAD+可降低血压和改善血管功能,其作用机制可能是通过激活SIRT3/IDH2信号通路降低内皮细胞氧化应激水平. |
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| AbstractList | 目的探讨烟酰胺腺嘌呤二核苷酸在改善高血压血管内皮损伤中的作用及其分子机制。方法利用渗透泵构建高血压小鼠模型，将C57BL/6J小鼠随机分为生理盐水组（Saline）和高血压组（Ang Ⅱ），每天补充NAD+前体——烟酰胺单核苷酸（300 mg/kg），4周后检测小鼠血压、内皮舒张功能、脉搏波传导速度。采用迁移实验和划痕实验评估体外内皮细胞功能；采用免疫荧光染色法检测mtROS水平；采用RT-PCR检测mtDNA、SIRT3、异柠檬酸脱氢酶2（IDH2）的mRNA表达；采用酶联免疫吸附法检测8-羟基-2'-脱氧鸟苷的水平；采用Western blot法检测p-eNOS、eNOS、SIRT3、IDH2蛋白表达水平。结果补充NMN降低了高血压小鼠血压（P<0.001），改善内皮功能和动脉僵硬度（P<0.001）；体外实验中，NMN可改善Ang Ⅱ刺激所致的内皮细胞舒张功能下降（P<0.05）和减轻线粒体氧化应激水平（P<0.001）。机制上，NMN提升了SIRT3活性（P<0.001），进而增强了IDH的活性（P<0.001），从而改善内皮细胞氧化应激水平；相反，敲低IDH2后将减弱SIRT3改善内皮功能的作用（P<0.001）。结论NAD+可降低血压和改善血管功能，其作用机制可能是通过激活SIRT3/IDH2信号通路降低内皮细胞氧化应激水平。 R544.1; [目的]探讨烟酰胺腺嘌呤二核苷酸在改善高血压血管内皮损伤中的作用及其分子机制.[方法]利用渗透泵构建高血压小鼠模型,将C57BL/6J小鼠随机分为生理盐水组(Saline)和高血压组(Ang Ⅱ),每天补充NAD+前体——烟酰胺单核苷酸(300 mg/kg),4周后检测小鼠血压、内皮舒张功能、脉搏波传导速度.采用迁移实验和划痕实验评估体外内皮细胞功能;采用免疫荧光染色法检测mtROS水平;采用RT-PCR检测mtDNA、SIRT3、异柠檬酸脱氢酶2(IDH2)的mRNA表达;采用酶联免疫吸附法检测8-羟基-2'-脱氧鸟苷的水平;采用Western blot法检测p-eNOS、eNOS、SIRT3、IDH2蛋白表达水平.[结果]补充NMN降低了高血压小鼠血压(P<0.001),改善内皮功能和动脉僵硬度(P<0.001);体外实验中,NMN可改善Ang Ⅱ刺激所致的内皮细胞舒张功能下降(P<0.05)和减轻线粒体氧化应激水平(P<0.001).机制上,NMN提升了SIRT3活性(P<0.001),进而增强了IDH的活性(P<0.001),从而改善内皮细胞氧化应激水平;相反,敲低IDH2后将减弱SIRT3改善内皮功能的作用(P<0.001).[结论]NAD+可降低血压和改善血管功能,其作用机制可能是通过激活SIRT3/IDH2信号通路降低内皮细胞氧化应激水平. |
| Abstract_FL | [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. |
| Author | 吴杏 刘张弛 朱秋霞 张建宁 张美信 陶军 丘雨旻 陈曦 |
| AuthorAffiliation | 中山大学附属第一医院高血压血管病科,广东 广州 510080 |
| AuthorAffiliation_xml | – name: 中山大学附属第一医院高血压血管病科,广东 广州 510080 |
| Author_FL | ZHANG Jianning QIU Yumin ZHANG Meixin LIU Zhangchi TAO Jun WU Xing CHEN Xi ZHU Qiuxia |
| Author_FL_xml | – sequence: 1 fullname: QIU Yumin – sequence: 2 fullname: CHEN Xi – sequence: 3 fullname: ZHANG Jianning – sequence: 4 fullname: LIU Zhangchi – sequence: 5 fullname: ZHU Qiuxia – sequence: 6 fullname: ZHANG Meixin – sequence: 7 fullname: TAO Jun – sequence: 8 fullname: WU Xing |
| Author_xml | – sequence: 1 fullname: 丘雨旻 – sequence: 2 fullname: 陈曦 – sequence: 3 fullname: 张建宁 – sequence: 4 fullname: 刘张弛 – sequence: 5 fullname: 朱秋霞 – sequence: 6 fullname: 张美信 – sequence: 7 fullname: 陶军 – sequence: 8 fullname: 吴杏 |
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| DOI | 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).20241122.001 |
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| DocumentTitle_FL | NAD+Ameliorates Endothelial Dysfunction in Hypertension via Activation of SIRT3/IDH2 Signal Pathway |
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| Keywords | nicotinamide adenine dinucleotide 高血压 血管内皮损伤 烟酰胺腺嘌呤二核苷酸 氧化应激 hypertension vascular endothelial injury oxidative stress SIRT3 |
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| Publisher | 中山大学附属第一医院高血压血管病科,广东 广州 510080 Editorial Office of Journal of Sun Yat-sen University |
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| Snippet | R544.1; [目的]探讨烟酰胺腺嘌呤二核苷酸在改善高血压血管内皮损伤中的作用及其分子机制.[方法]利用渗透泵构建高血压小鼠模型,将C57BL/6J小鼠随机分为生理盐水组(Saline)和高血压组(Ang Ⅱ),每天补充NAD+前体——烟酰胺单核苷酸(300... 目的探讨烟酰胺腺嘌呤二核苷酸在改善高血压血管内皮损伤中的作用及其分子机制。方法利用渗透泵构建高血压小鼠模型，将C57BL/6J小鼠随机分为生理盐水组（Saline）和高血压组（Ang Ⅱ），每天补充NAD+前体——烟酰胺单核苷酸（300... |
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| SubjectTerms | SIRT3 氧化应激 烟酰胺腺嘌呤二核苷酸 血管内皮损伤 高血压 |
| Title | NAD+激活SIRT3/IDH2信号通路改善高血压血管内皮功能障碍 |
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