C3b/VSIG4信号抑制巨噬细胞STING介导的坏死性凋亡减轻缺血再灌注肝损伤的机制研究

注册号:

Registration number:

ChiCTR2600120455 

最近更新日期:

Date of Last Refreshed on:

2026-03-16 08:31:45 

注册时间:

Date of Registration:

2026-03-16 00:00:00 

注册号状态:

补注册

Registration Status:

Retrospective registration

注册题目:

C3b/VSIG4信号抑制巨噬细胞STING介导的坏死性凋亡减轻缺血再灌注肝损伤的机制研究

Public title:

Mechanism of C3b/VSIG4 signaling inhibiting macrophage STING-mediated necrotizing apoptosis in attenuating ischemia-reperfusion liver injury

注册题目简写:

English Acronym:

研究课题的正式科学名称:

C3b/VSIG4信号抑制巨噬细胞STING介导的坏死性凋亡减轻缺血再灌注肝损伤的机制研究

Scientific title:

Mechanism of C3b/VSIG4 signaling inhibiting macrophage STING-mediated necrotizing apoptosis in attenuating ischemia-reperfusion liver injury

研究课题代号(代码):

Study subject ID:

在二级注册机构或其它机构的注册号:

The registration number of the Partner Registry or other register:

申请注册联系人:

谭蔚锋 

研究负责人:

谭蔚锋 

Applicant:

Weifeng Tan 

Study leader:

Weifeng Tan 

申请注册联系人电话:

Applicant telephone:

+86 18918811855

研究负责人电话:

Study leader's
telephone:

+86 18918811855

申请注册联系人传真 :

Applicant Fax:

研究负责人传真:

Study leader's fax:

申请注册联系人电子邮件:

Applicant E-mail:

twf1231@163.com

研究负责人电子邮件:

Study leader's E-mail:

20537@renji.com

申请单位网址(自愿提供):

Applicant website(voluntary supply):

研究负责人网址(自愿提供):

Study leader's website(voluntary supply):

申请注册联系人通讯地址:

上海市普陀区新村路389号

研究负责人通讯地址:

上海市普陀区新村路389号

Applicant address:

No. 389, Xincun Road, Putuo District, Shanghai, China

Study leader's address:

No. 389, Xincun Road, Putuo District, Shanghai

申请注册联系人邮政编码:

Applicant postcode:

研究负责人邮政编码:

Study leader's postcode:

申请人所在单位:

上海市同济医院(同济大学附属同济医院)

Applicant's institution:

Shanghai Tongji Hospital(Tongji Hospital of Tongji University)

研究负责人所在单位:

上海市同济医院

Affiliation of the Leader:

Tongji Hospital of Tongji University

是否获伦理委员会批准:

Approved by ethic committee:

Yes

伦理委员会批件文号:

Approved No. of ethic committee:

(同)伦审第(K-2024-055)号

伦理委员会批件附件:

Approved file of Ethical Committee:

查看附件View

批准本研究的伦理委员会名称:

上海市同济医院伦理委员会

Name of the ethic committee:

ShanghaiTongji Hospital (Tongji Hospital of Tongji University) Ethics Committee

伦理委员会批准日期:

Date of approved by ethic committee:

2024-10-19 00:00:00

伦理委员会联系人:

宣淼

Contact Name of the ethic committee:

Xuan Miao

伦理委员会联系地址:

上海市普陀区新村路389号

Contact Address of the ethic committee:

No. 389, Xincun Road, Putuo District, Shanghai

伦理委员会联系人电话:

Contact phone of the ethic committee:

+86 21 66111243

伦理委员会联系人邮箱:

Contact email of the ethic committee:

tongjilunli2012@163.com

研究实施负责(组长)单位:

上海市同济医院

Primary sponsor:

Tongji Hospital of Tongji University

研究实施负责(组长)单位地址:

上海市普陀区新村路389号

Primary sponsor's address:

No. 389, Xincun Road, Putuo District, Shanghai

试验主办单位(项目批准或申办者):

Secondary sponsor:

国家:

中国

省(直辖市):

上海市

市(区县):

Country:

China

Province:

Shanghai

City:

单位(医院):

上海市同济医院

具体地址:

上海市普陀区新村路389号

Institution
hospital:

Tongji Hospital of Tongji University

Address:

No. 389, Xincun Road, Putuo District, Shanghai

经费或物资来源:

人才引进

Source(s) of funding:

Talent Introduction

研究疾病:

肝脏缺血再灌注损伤  

Target disease:

Liver ischemia-reperfusion injury

研究疾病代码:

Target disease code:

研究类型:

观察性研究

Study type:

Observational study

研究所处阶段:

其它 

Study phase:

N/A

研究设计:

病例对照研究 

Study design:

Case-Control study 

研究目的:

(1)首先,基于肝损伤患者外周血(血清/血浆)中蛋白质组的检测确定差异表达的蛋白谱,明确差异表达蛋白与患者肝功指标及疾病转归的相关性。 (2)其次,基于STING髓系敲除小鼠和LIRI小鼠模型,体外肝细胞-BMDM共培养技术,明确STING介导的BMDM坏死性凋亡促进肝损伤炎症损伤。 (3)再次,根据差异表达蛋白谱,利用髓系敲除小鼠、C3b重组蛋白等,明确C3b是否可减轻肝损伤,并且与抑制STING信号介导的巨噬细胞坏死性凋亡有关。 (4)最后,通过敲降/过表达PDK2,明确C3b是否通过PDK2抑制丙酮酸线粒体代谢,阻断巨噬细胞坏死性凋亡。  

Objectives of Study:

(1) Firstly, based on the detection of proteome in peripheral blood (serum/plasma) of patients with liver injury, the differentially expressed protein profile was determined, and the correlation between differentially expressed proteins and liver function indexes and disease outcomes of patients was clearly defined. (2) Secondly, based on STING myeloma knockout mouse and LIRI mouse models, in vitro hepatocellular BMDM co-culture technology was used to confirm that STING-mediated BMDM necrotic apoptosis promotes liver injury inflammation. (3) Third, according to the differential expression protein profile, myeloid knockout mice and C3b recombinant protein were used to determine whether C3b can alleviate liver injury and is related to the inhibition of STING signaling mediated necrotic apoptosis of macrophages. (4) Finally, by knockdown/overexpression of PDK2, it was determined whether C3b inhibited pyruvate mitochondrial metabolism through PDK2 and blocked necrotic apoptosis of macrophages.

药物成份或治疗方案详述:

 

Description for medicine or protocol of treatment in detail:

 

纳入标准:

Inclusion criteria

排除标准:

1.慢性肝损伤患者;
2.孕妇及哺乳期妇女、双相情感障碍、精神分裂症等严重精神病;
3.小于18岁或者大于80岁患者;

Exclusion criteria:

1.Patients with chronic liver injury;
2.Pregnant and lactating women, bipolar disorder, schizophrenia and other serious mental disorders;
3.Patients younger than 18 years or older than 80 years;

研究实施时间:

Study execute time:

From 2024-10-22 00:00:00 To 2026-12-31 00:00:00  

征募观察对象时间:

Recruiting time:

From 2024-10-25 00:00:00 To 2025-12-31 00:00:00

干预措施:

Interventions:

组别:

观察组

样本量:

5

Group:

Observation group

Sample size:

干预措施:

干预措施代码:

Intervention:

None

Intervention code:

组别:

对照组

样本量:

5

Group:

Control group

Sample size:

干预措施:

干预措施代码:

Intervention:

None

Intervention code:

组别:

急性肝损伤组

样本量:

20

Group:

Acute liver injury group

Sample size:

干预措施:

干预措施代码:

Intervention:

None

Intervention code:

研究实施地点:

Countries of recruitment and research settings:

国家:

中国

省(直辖市):

上海市 

市(区县):

 

Country:

China

Province:

Shanghai

City:

单位(医院):

上海市同济医院 

单位级别:

三级甲等 

Institution
hospital:

Tongji Hospital of Tongji University

Level of the institution:

Tertiary A

测量指标:

Outcomes:

指标中文名:

蛋白标志物

指标类型:

主要指标

Outcome:

Protein marker

Type:

Primary indicator

测量时间点:

术前、术后第三天、术后第七天

测量方法:

质谱检测、ELASA检测

Measure time point of outcome:

Before surgery, the third day after surgery, and the seventh day after surgery

Measure method:

Mass spectrometry detection, ELASA detection

采集人体标本:

Collecting sample(s)
from participants:

标本中文名:

血浆

组织:

Sample Name:

Serum

Tissue:

人体标本去向

使用后保存  

说明

Fate of sample:

Preservation after use  

Note:

征募研究对象情况:

Recruiting status:

正在进行

Recruiting

年龄范围:

Participant age:

最小 Min age 18 years
最大 Max age 80 years

性别:

男女均可

Gender:

Both

随机方法(请说明由何人用什么方法产生随机序列):

Randomization Procedure (please state who generates the random number sequence and by what method):

None

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

不公开/Private

盲法:

Blinding:

None

是否共享原始数据:

IPD sharing

是Yes

共享原始数据的方式(说明:请填入公开原始数据日期和方式,如采用网络平台,需填该网络平台名称和网址):

论文发表后,邮件向研究者申请同意后共享原始数据;

The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url):

After the paper is published, the original data will be shared after applying to the researcher for approval by email;

数据采集和管理(说明:数据采集和管理由两部分组成,一为病例记录表(Case Record Form, CRF),二为电子采集和管理系统(Electronic Data Capture, EDC),如ResMan即为一种基于互联网的EDC:

Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture:

None

数据与安全监察委员会:

Data and Safety Monitoring Committee:

无/No

注册人:

Name of Registration:

 2026-03-16 08:30:06