课题基金基金详情
WR1065通过ASK1/JNK通路防治种植体周放射性微血管损伤的研究
结题报告
批准号:
82001090
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
黄波
依托单位:
学科分类:
牙缺损、缺失修复及牙颌畸形的矫治
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
黄波
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中文摘要
头颈部恶性肿瘤的放射治疗易造成颌骨放射性骨损伤,影响种植体骨结合和留存率。最新研究显示促进局部微血管再生是减轻放射性骨损伤的关键。高压氧和抗氧化治疗及最新的基因治疗等因其生物安全性、治疗的有效性等问题,运用较为局限。WR1065是FDA批准唯一可以用于临床的泛细胞保护剂。申请人前期发现WR1065能够减轻放射对血管内皮细胞的成管效果的影响,但具体机制尚不明确。本项目首先将利用SD大鼠颌骨植入种植体模型,研究WR1065能否通过JNK通路减轻放射对颌骨及种植体周微血管的损伤,进而提高放射后种植体成功率和预防放射对已有种植体的损伤;利用MAPK(MAPK通路包含JNK通路)信号通路PCR芯片分析WR1065在血管内皮细胞中发挥作用的关键基因(推测为ASK1);最后通过构建关键基因(ASK1)的过表达和沉默的病毒,转染血管内皮细胞,探究WR1065的作用及其机制,为其临床使用提供基础数据。
英文摘要
Radiotherapy of head and neck cancer easily leads to radiation-induced bone injury of jaw, which affects the osseointegration and success rate of implants. Recent studies have demonstrated that promoting local microvascular regeneration is the key to reducing radiation-induced bone injury. The traditional method including hyperbaric oxyge and antioxidant therapy and the gene therapy are limited used because of their biological safety and uncertainty of therapeutic effect. WR1065 is the only broad-spectrum cytoprotective agent approved by FDA for clinical use. Our previous study found that WR1065 could reduce the side effect of radiation on vascular endothelial cells, but the mechanism is not clear. In this experiment, we will first use dental implant model of jaw to study whether WR1065 can reduce the injury of jaw and microvascular around the dental implant by JNK pathway, whether it could improve the success rate of the implant in radiation bone and reduce the injury caused by radiation on the succeed implants. We will also use the MAPK (MAPK pathway including JNK pathway) signal pathway PCR chip to analyze the key genes (presumably ASK1) of WR1065 playing a role in vascular endothelial cells. Finally, we will construct the over expression and silencing viruses of key gene (ASK1),then use the viruses to transfect vascular endothelial cells, exploring the role and mechanism of WR1065, which will provide basic data for clinical use.
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DOI:10.1016/j.tice.2022.101985
发表时间:2022-11
期刊:Tissue & cell
影响因子:2.6
作者:Bo Huang;Yixuan Jiang;Liang Zhang;Bo Yang;Yanjun Guo;Xingmei Yang;P. Gong
通讯作者:Bo Huang;Yixuan Jiang;Liang Zhang;Bo Yang;Yanjun Guo;Xingmei Yang;P. Gong
DOI:https://doi.org/10.1155/2023/1440889
发表时间:2023
期刊:Journal of Oncology
影响因子:--
作者:Nan Huang;Peihan Wang;Ping Gong;Bo Huang
通讯作者:Bo Huang
DOI:10.3390/jcm12030920
发表时间:2023-01-24
期刊:Journal of clinical medicine
影响因子:3.9
作者:
通讯作者:
DOI:10.1155/2021/4758364
发表时间:2021
期刊:Journal of oncology
影响因子:--
作者:Li Y;Wang X;Pang Y;Wang S;Luo M;Huang B
通讯作者:Huang B
国内基金
海外基金