Neuroprotection of NAD+ and NBP against ischemia/reperfusion brain injury is associated with restoration of sirtuin-regulated metabolic homeostasis

NAD+激酶 神经保护 SIRT3 烟酰胺腺嘌呤二核苷酸 锡尔图因 缺血 药理学 医学 再灌注损伤 体内 氧化应激 脑缺血 化学 麻醉 生物化学 内分泌学 内科学 生物 生物技术
作者
Xinxin Wang,Guang-Hui Mao,Qiqi Li,Jie Tang,Hua Zhang,Kanglin Wang,Lei Wang,Hong Ni,Rui Sheng,Zheng‐Hong Qin
出处
期刊:Frontiers in Pharmacology [Frontiers Media SA]
卷期号:14 被引量:10
标识
DOI:10.3389/fphar.2023.1096533
摘要

Background: Ischemic stroke seriously threatens human health because of high rates of morbidity, mortality and disability. This study compared the effects of nicotinamide adenine dinucleotide (NAD+) and butylphthalide (NBP) on in vitro and in vivo ischemic stroke models. Methods: Transient middle cerebral artery occlusion/reperfusion (t-MCAO/R) model was established in mice, and the cultured primary cortical neurons were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). Cerebral infarct volume, neurobehavioral indices, antioxidant activity, ATP level and lactic acid content were determined. The neuroprotective effects of NAD+ or NBP were compared using sirtuin inhibitor niacinamide (NAM). Results: Intraperitoneal injection of NBP within 4 h or intravenous injection of NAD+ within 1 h after t-MCAO/R significantly reduced the volume of infarcts, cerebral edema, and neurological deficits. Administration of NAD+ and NBP immediately after t-MCAO/R in mice showed similar neuroprotection against acute and long-term ischemic injury. Both NAD+ and NBP significantly inhibited the accumulation of MDA and H2O2 and reduced oxidative stress. NAD+ was superior to NBP in inhibiting lipid oxidation and DNA damage. Furthermore, although both NAD+ and NBP improved the morphology of mitochondrial damage induced by ischemia/reperfusion, NAD+ more effectively reversed the decrease of ATP and increase of lactic acid after ischemia/reperfusion compared with NBP. NAD+ but not NBP treatment significantly upregulated SIRT3 in the brain, but the sirtuin inhibitor NAM could abolish the protective effect of NAD+ and NBP by inhibiting SIRT1 or SIRT3. Conclusions: These results confirmed the protective effects of NAD+ and NBP on cerebral ischemic injury. NBP and NAD+ showed similar antioxidant effects, while NAD+ had better ability in restoring energy metabolism, possibly through upregulating the activity of SIRT1 and SIRT3. The protection provided by NBP against cerebral ischemia/reperfusion may be achieved through SIRT1.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
Lcs发布了新的文献求助30
1秒前
李爱国应助guojingjing采纳,获得10
1秒前
共享精神应助乌禅采纳,获得10
1秒前
AKKKK发布了新的文献求助30
1秒前
图图完成签到,获得积分20
2秒前
2秒前
2秒前
3秒前
搞什么搞完成签到,获得积分10
3秒前
Carrido发布了新的文献求助10
3秒前
葛儿完成签到 ,获得积分10
4秒前
猕猴桃猴发布了新的文献求助10
5秒前
yeah完成签到,获得积分10
5秒前
冷静的忆秋完成签到,获得积分10
6秒前
7秒前
星途完成签到,获得积分10
7秒前
金平卢仙发布了新的文献求助10
7秒前
Liang发布了新的文献求助10
7秒前
8秒前
上好佳发布了新的文献求助20
8秒前
JamesPei应助搞什么搞采纳,获得30
8秒前
9秒前
帅气白云完成签到,获得积分10
12秒前
上官若男应助科研采纳,获得10
13秒前
犹豫的白桃完成签到,获得积分10
13秒前
WillZ完成签到,获得积分20
14秒前
guojingjing发布了新的文献求助10
14秒前
FashionBoy应助errui采纳,获得10
16秒前
机灵的煎蛋完成签到,获得积分10
16秒前
18秒前
alec发布了新的文献求助10
18秒前
司徒元瑶完成签到 ,获得积分10
18秒前
18秒前
莎莎完成签到,获得积分10
19秒前
chendumo完成签到,获得积分10
19秒前
顾矜应助zhen采纳,获得10
19秒前
20秒前
英姑应助麻辣烫采纳,获得30
20秒前
22秒前
eason发布了新的文献求助10
23秒前
高分求助中
Continuum Thermodynamics and Material Modelling 3000
Production Logging: Theoretical and Interpretive Elements 2700
Les Mantodea de Guyane Insecta, Polyneoptera 1000
Structural Load Modelling and Combination for Performance and Safety Evaluation 1000
Conference Record, IAS Annual Meeting 1977 820
電気学会論文誌D(産業応用部門誌), 141 巻, 11 号 510
Typology of Conditional Constructions 500
热门求助领域 (近24小时)
化学 材料科学 生物 医学 工程类 有机化学 生物化学 物理 纳米技术 计算机科学 内科学 化学工程 复合材料 基因 遗传学 物理化学 催化作用 量子力学 光电子学 冶金
热门帖子
关注 科研通微信公众号,转发送积分 3570690
求助须知:如何正确求助?哪些是违规求助? 3141392
关于积分的说明 9442819
捐赠科研通 2842740
什么是DOI,文献DOI怎么找? 1562418
邀请新用户注册赠送积分活动 731079
科研通“疑难数据库(出版商)”最低求助积分说明 718290