Period1基因变体调控生物钟分子发条对卒中后血压浸渍的作用机制

批准号:
81970348
项目类别:
面上项目
资助金额:
55.0 万元
负责人:
何明利
依托单位:
学科分类:
血压调节异常与高血压病
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
何明利
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中文摘要
卒中后血压浸渍(BPD)是卒中复发的主要残余风险之一,阐明其发病机制意义重大。前期发现,卒中后生物钟核心基因CLOCK和BMAL1转录因子高表达同步震荡,但Period1(PER1)驱动子在一过性高表达后下降并持续至第二个黎明不再复升。人群筛查发现,PER1基因变体(rs2253820)与卒中后BPD高度关联。基于前期结果和生物钟自主转录-翻译反馈环调控机制,提出PER1基因变体引发生物钟分子发条机能障碍导致卒中后BPD的新机制,拟采用慢病毒过表达/沉默载体、基因敲除/过表达、EMSA、Chip等技术,探索卒中后BPD中PER1基因变体对其表达蛋白的影响及其与BMAL1、CLOCK基因的互作机制和作用靶点,临床研究阐明PER1基因变体与卒中后BPD的关系及其对卒中预后的预测价值。PER1基因变体对卒中后BPD的作用机制申请者未见报道,本研究可为卒中后BPD的防治提供新理论和药物作用新靶点。
英文摘要
Post-stroke blood pressure dip (BPD) is one of the major residual risks of stroke recurrence, and it is important to elucidate its pathogenesis.Previous studies have found that the high expression of the transcriptional factors CLOCK and BMAL1 are synchronously oscillated after stroke, but the Period1 (PER1) kinesin rapidly declines after transient high expression and continues until the second dawn no longer rises. Population screening revealed that the PER1 gene variant (rs2253820) was highly correlated with post-stroke BPD. Based on previous results and the regulation mechanism of mautonomous transcription-translation feedback loop of the biological clock, we proposed a new mechanism that the PER1 gene variant triggers the dysfunction of circadian rhythm and leads to post-stroke BPD. Using lentiviral overexpression / silencing vector, gene knockout / over expression, EMSA, Chip and other techniques to explore the effect of PER1 gene variant on its expressed protein and its interaction mechanism and action target with BMAL1,CLOCK gene in BPD after stroke. Clinical research to elucidate the relationship between PER1 gene variants and post-stroke BPD and its predictive value for stroke prognosis.The mechanism of PER1 variant on post-stroke BPD has not been reported. This study can provide new theoretical and pharmacological targets for the prevention and treatment of BPD after stroke.
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
DOI:--
发表时间:2020
期刊:国际脑血管病杂志
影响因子:--
作者:金晶;刘雨朦;葛建;张栋;陈思源;何明利
通讯作者:何明利
Optimal blood pressure levels in different phases of peripheral thrombolysis period in acute ischemic stroke
急性缺血性脑卒中外周溶栓期不同阶段的最佳血压水平
DOI:10.1097/hjh.0000000000002812
发表时间:2021-07-01
期刊:JOURNAL OF HYPERTENSION
影响因子:4.9
作者:He, Mingli;Wang, Hongrui;Wang, Yibo
通讯作者:Wang, Yibo
DOI:--
发表时间:2021
期刊:国际脑血管病杂志
影响因子:--
作者:金晶;刘雨朦;张栋;葛建;黄璟;何明利
通讯作者:何明利
DOI:10.1111/jch.14385
发表时间:2021-12
期刊:Journal of clinical hypertension (Greenwich, Conn.)
影响因子:--
作者:He M;Cui B;Wang J;Xiao X;Wu T;Wang M;Yang R;Zhang B;Xu B;He X;Zhang G;Niu X;Li Z;Wang B;Xu B;Hui R;Wang Y
通讯作者:Wang Y
DOI:--
发表时间:2021
期刊:国际脑血管病杂志
影响因子:--
作者:陈思源;何明利;金晶;葛建;张栋;施海媛;刘雨朦
通讯作者:刘雨朦
国内基金
海外基金
