课题基金基金详情
Peroxiredoxin2介导的内源性抗氧化在氢气对蛛网膜下腔出血后早期脑保护中的作用及机制研究
结题报告
批准号:
81971127
项目类别:
面上项目
资助金额:
55.0 万元
负责人:
庄宗
依托单位:
学科分类:
脑血管结构、功能异常及相关疾病
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
庄宗
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中文摘要
早期脑损伤(EBI)是影响蛛网膜下腔出血(SAH)预后的重要因素。氧化应激在SAH后的EBI中起重要作用。氢气(H2)被证明是理想的选择性抗氧化(外源性抗氧化)治疗剂,我们既往研究发现H2治疗能减轻SAH后的EBI,但仍有诸多疑问并非其外源性抗氧化机制能解释。过氧化物还原酶(Prx)家族在内源性抗氧化中起重要作用。我们研究发现SAH患者脑脊液中Prx2明显升高。氧化应激的关键枢纽核因子E2相关因子2(Nrf2)是Prx2上游核转录因子。结合文献,我们提出假说:SAH后H2可激活Nrf2/Prx2轴启动内源性抗氧化减轻SAH后EBI。本课题拟通过体内、体外模型在上下游分别用基因敲除、RNA干扰及荧光素酶报告基因实验,探索H2调控Nrf2/Prx2轴的内源性抗氧化机制。本课题旨在阐明H2的抗氧化机制,并结合我们已启动的H2治疗SAH患者的临床试验为H2治疗的临床转化提供理论基础。
英文摘要
Early brain injury (EBI) is a significant contributor to the poor outcome after subarachnoid hemorrhage (SAH). Oxidative stress plays an important role in EBI following SAH. The protective effect of hydrogen (H2) has been widely studied since H2 has been deemed as an exogenous selective radical scavenger. Our previous studies found that H2 therapy can reduce EBI after SAH. But there are still many problems that cannot be explained by the exogenous mechanism of H2. Peroxiredoxin family play vital role in the endogenous antioxidant effect. Previously, we found that Prx2 increased dramatically in the cerebrospinal fluid of SAH patients. Nuclear factor E2-related factor 2 (Nrf2), an important nuclear transcription factor of Prx2, is a key factor in oxidative stress. Hence, we assume that H2 could activate Nrf2/prx2 axis alleviating EBI following SAH. In order to verify this endogenous mechanism, we will regulate Nrf2 and prx2 both in vivo and in vitro via transgenetic mice, RNA interference and gene overexpression technique. And the luciferase expression plasmid controlled by Nrf2 promoter will be used to illuminate the molecular mechanism of Nrf2 activation. Moreover, combined with our clinical trial of H2 treatment on SAH patients, our results could be the primary stage for the clinical translation of H2 treatment.
期刊论文列表
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专利列表
DOI:10.1016/j.bbrc.2023.04.072
发表时间:2023-04
期刊:Biochemical and biophysical research communications
影响因子:3.1
作者:Zheng Peng;Xiaojian Li;Cong Pang;Jia-Tong Zhang;Qigai Zhu;Jianling Sun;Juan Wang;Bo-qiang Cao;Yu-hua Zhang;Yue Lu;Wei Li;C. Hang;Zhuang Zong
通讯作者:Zheng Peng;Xiaojian Li;Cong Pang;Jia-Tong Zhang;Qigai Zhu;Jianling Sun;Juan Wang;Bo-qiang Cao;Yu-hua Zhang;Yue Lu;Wei Li;C. Hang;Zhuang Zong
DOI:10.1155/2022/9148257
发表时间:2022
期刊:OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
影响因子:--
作者:Ding, Peng-Fei;Zhu, Qi;Sheng, Bin;Yang, Heng;Xu, Hua-Jie;Tao, Tao;Peng, Zheng;Chen, Xiang-Xin;Li, Xiao-Jian;Zhou, Yan;Zhang, Hua-Sheng;Gao, Yong-Yue;Zhuang, Zong;Hang, Chun-Hua;Li, Wei
通讯作者:Li, Wei
DOI:10.3390/brainsci12091264
发表时间:2022-09-19
期刊:BRAIN SCIENCES
影响因子:3.3
作者:Zhuang, Zong;Zhu, Qi;Liu, Xun-Zhi;Ling, Hai-Ping;Na, Shi-Jie;Liu, Tao;Zhang, Yu-Hua;Hang, Chun-Hua;Liu, Kai-Dong;Zhang, Qing-Rong
通讯作者:Zhang, Qing-Rong
Peroxiredoxin 2 Is a Potential Objective Indicator for Severity and the Clinical Status of Subarachnoid Hemorrhage Patients.
过氧蛋白2是严重程度和蛛网膜下腔出血患者的临床状况的潜在客观指标。
DOI:10.1155/2023/5781180
发表时间:2023
期刊:DISEASE MARKERS
影响因子:--
作者:Peng, Zheng;Pang, Cong;Li, Xiao-Jian;Zhang, Hua-Sheng;Zhang, Jia-Tong;Zhu, Qi;Xu, Hua-Jie;Gao, Yong-Yue;Zhuang, Zong;Li, Wei;Zhang, Qing-Rong;Lu, Yue;Hang, Chun-Hua
通讯作者:Hang, Chun-Hua
DOI:10.1016/j.freeradbiomed.2024.02.002
发表时间:2024-02-21
期刊:FREE RADICAL BIOLOGY AND MEDICINE
影响因子:7.4
作者:Peng,Zheng;Ye,Qing-Song;Zhuang,Zong
通讯作者:Zhuang,Zong
NF-κB/Bcl-xL在氢气对蛛网膜下腔出血后早期脑保护中的作用机制研究
  • 批准号:
    81400980
  • 项目类别:
    青年科学基金项目
  • 资助金额:
    23.0万元
  • 批准年份:
    2014
  • 负责人:
    庄宗
  • 依托单位:
国内基金
海外基金