中国临床试验注册中心 - 世界卫生组织国际临床试验注册平台一级注册机构

注册号： Registration number：	ChiCTR2500111872
最近更新日期： Date of Last Refreshed on：	2025-11-06 19:09:12
注册时间： Date of Registration：	2025-11-06 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	HMGB1抑制剂甘草甜素通过调控Treg改善静脉溶栓诱导的血脑屏障损伤的研究
Public title：	Study on HMGB1 Inhibitor Glycyrrhizin Ameliorating Blood-Brain Barrier Damage Induced by Intravenous Thrombolysis through Regulation of Treg Cells
注册题目简写：
English Acronym：
研究课题的正式科学名称：	HMGB1抑制剂甘草甜素通过调控Treg改善静脉溶栓诱导的血脑屏障损伤的研究
Scientific title：	Study on HMGB1 Inhibitor Glycyrrhizin Ameliorating Blood-Brain Barrier Damage Induced by Intravenous Thrombolysis through Regulation of Treg Cells
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：	董晓梦	研究负责人：	张祥建
Applicant：	Xiaomeng Dong	Study leader：	Xiangjian Zhang
申请注册联系人电话： Applicant telephone：	+86 131 4942 8689	研究负责人电话： Study leader's telephone：	+86 157 3218 9189
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：	doctor_dxm1989@126.com	研究负责人电子邮件： Study leader's E-mail：	zhang6xj@aliyun.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：	河北省石家庄市新华区中华北大街309号	研究负责人通讯地址：	河北省石家庄市新华区中华北大街309号
Applicant address：	309 Zhonghua Street North, Xinhua District, Shijiazhuang, Hebei	Study leader's address：	309 Zhonghua Street North, Xinhua District, Shijiazhuang, Hebei
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：	河北医科大学第二医院
Applicant's institution：	The Second Hospital of Hebei Medical University
研究负责人所在单位：	河北医科大学第二医院
Affiliation of the Leader：	The Second Hospital of Hebei Medical University

是否获伦理委员会批准：	是
Approved by ethic committee：	Yes
伦理委员会批件文号： Approved No. of ethic committee：	2025-R808	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：	河北医科大学第二医院科研伦理委员会
Name of the ethic committee：	Research Ethics Committee of The Second Hospital of Hebei Medical University
伦理委员会批准日期： Date of approved by ethic committee：	2025-10-17 00:00:00
伦理委员会联系人：	安雯婷
Contact Name of the ethic committee：	Wenting An
伦理委员会联系地址：	河北省石家庄市新华区和平西路215号
Contact Address of the ethic committee：	215 Heping Road West, Xinhua District, Shijiazhuang, Hebei
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 158 0321 0578	伦理委员会联系人邮箱： Contact email of the ethic committee：

研究实施负责（组长）单位：

河北医科大学第二医院

Primary sponsor：

The Second Hospital of Hebei Medical University

研究实施负责（组长）单位地址：

河北省石家庄市新华区中华北大街309号

Primary sponsor's address：

309 Zhonghua Street North, Xinhua District, Shijiazhuang, Hebei

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	石家庄	市(区县)：	石家庄
Country：	China	Province：	Hebei	City：	Shijiazhuang
单位(医院)：	河北医科大学第二医院	具体地址：	河北省石家庄市新华区中华北大街309号
Institution hospital：	The Second Hospital of Hebei Medical University	Address：	309 Zhonghua Street North, Xinhua District, Shijiazhuang, Hebei

经费或物资来源：

博士研究生课题经费

Source(s) of funding：

Research funds for doctoral students

研究疾病：

缺血性脑卒中

Target disease：

Ischemic stroke

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：

中风是全球神经系统健康损失首要因素，缺血性卒中（IS）约占 70%，我国 IS 负担较重。静脉溶栓治疗是 IS早期再灌注的重要方法，但治疗窗窄且易引发血脑屏障（BBB）损伤致出血转化（HT）。调节性T细胞（Treg）对IS有保护作用，可改善BBB损伤，但静脉溶栓治疗会使其数量减少，且 Treg在溶栓药rtPA等诱导的 BBB 损伤中的具体机制不明。高迁移率族蛋白1（HMGB1）在 IS 和 rtPA 治疗中会加剧 BBB 损伤，对Treg具有负性调节作用。本研究聚焦 HMGB1 抑制剂甘草甜素通过调控 Treg改善静脉溶栓诱导的BBB损伤的机制。将结合双光子荧光活体成像、激光共聚焦、单细胞 RNA 测序等技术，开展在体和体外实验，从分子、细胞、组织层面，研究甘草甜素对 Treg 数量、功能及迁徙的影响，以及 Treg 改善 BBB 损伤的机制。本研究有望阐明 HMGB1 - Treg-BBB损伤的关联，为提高静脉溶栓治疗的有效性和安全性、改善 IS 患者长期预后提供理论依据，为 IS 治疗策略创新提供新思路。

Objectives of Study：

Stroke is the leading cause of neurological impairment worldwide. Ischemic stroke (IS) accounts for approximately 70% of all strokes, and China bears a substantial burden of IS. Intravenous thrombolysis (IVT), particularly with recombinant tissue plasminogen activator (rtPA), is a cornerstone of early reperfusion therapy for IS. However, its clinical utility is limited by a narrow therapeutic window and the risk of hemorrhagic transformation (HT) secondary to blood-brain barrier (BBB) disruption.While regulatory T cells (Tregs) are known to be protective in IS and can ameliorate BBB injury, IVT paradoxically reduces their numbers. The precise role and mechanisms of Tregs in rtPA-induced BBB damage remain unclear. High mobility group box 1 (HMGB1), which is elevated in IS and further exacerbated by rtPA treatment, not only aggravates BBB injury but also negatively regulates Tregs.This study aims to investigate the mechanism by which glycyrrhizin, an HMGB1 inhibitor, ameliorates IVT-induced BBB damage through the modulation of Tregs. Utilizing a combination of in vivo and in vitro approaches, including two-photon fluorescence live imaging, confocal microscopy, and single-cell RNA sequencing, we will examine the effects of glycyrrhizin on Treg quantity, function, and migration at molecular, cellular, and tissue levels. Furthermore, we will elucidate the mechanisms through which Tregs confer protection against BBB injury.This research is expected to clarify the HMGB1-Treg-BBB injury axis, providing a theoretical foundation for enhancing the efficacy and safety of IVT, improving long-term outcomes for IS patients, and pioneering innovative therapeutic strategies for IS.

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

Inclusion criteria for the case group:
The subject has signed the informed consent form.
2. Meet the diagnostic criteria for acute cerebral infarction as stipulated in the "Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke (2023)".
3. Acute cerebral infarction occurred in the internal carotid artery system (anterior circulation), with an onset time of less than 4.5 hours.
4.18 years old ≤ 80 years old.
5. Received intravenous thrombolysis but no mechanical thrombectomy.
6. First-onset cerebral infarction or a history of previous cerebral infarction without remaining neurological deficits.

Inclusion criteria for the case control group:
The subject has signed the informed consent form.
2. Meet the diagnostic criteria for acute cerebral infarction as stipulated in the "Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke (2023)".
3. Acute cerebral infarction occurred in the internal carotid artery system (anterior circulation), with an onset time of less than 4.5 hours.
4.18 years old ≤ 80 years old.
5. No intravenous thrombolysis or mechanical thrombectomy was performed.
6. First-onset cerebral infarction or a history of previous cerebral infarction without remaining neurological deficits.

Inclusion criteria for the healthy control group:
The subject has signed the informed consent form.
2.18 years old <= age <=80 years old.
3. Blood routine test: Red blood cell count, MCHC, hemoglobin, white blood cell count, lymphocyte count, neutrophil count and monocyte count are all within the normal range.
4.TG, TC, HDL-C, LDL-C, blood glucose and glycated hemoglobin are within the normal range.

排除标准：

病例组排除标准： 1.头颅 CT 或 MRI 检查显示颅内出血性疾病（如出血性卒中、蛛网膜下腔出血、颅内血肿、硬膜外血肿）。 2.既往存在神经功能缺损症状，改良Rankin 评分（mRS）>=2 分。 3.患有严重心、肝、肾等重要器官功能障碍的患者。 4.患有恶性肿瘤、血液系统疾病、免疫系统疾病、结核病或中重度感染的患者。 5.既往有输血史、手术史及外伤史。 6.心电图异常的患者。 7.妊娠期或哺乳期妇女。 8.本研究期间，患者已入选或计划入选另一项临床药物或装置/干预性研究。病例对照组排除标准： 1.头颅 CT 或 MRI 检查显示颅内出血性疾病（如出血性卒中、蛛网膜下腔出血、颅内血肿、硬膜外血肿）。 2.既往存在神经功能缺损症状，改良Rankin 评分（mRS）>=2 分。 3.患有严重心、肝、肾等重要器官功能障碍的患者。 4.患有恶性肿瘤、血液系统疾病、免疫系统疾病、结核病或中重度感染的患者。 5.既往有输血史、手术史及外伤史。 6.心电图异常的患者。 7.进行静脉溶栓和血管内介入治疗的患者。 8.妊娠期或哺乳期妇女。 9.本研究期间，患者已入选或计划入选另一项临床药物或装置/干预性研究。健康对照组排除标准： 1.存在其他疾病：神经系统疾病（脑梗死、脑出血、多发性硬化等）；各种急慢性消化系统疾病；循环系统疾病（冠心病、心力衰竭、房颤）；呼吸系统疾病（慢性阻塞性肺疾病、慢性支气管炎、哮喘）；代谢性疾病（肥胖、高脂血症、糖尿病、代谢综合征、骨质疏松症）；泌尿系统疾病（慢性肾脏病、肾衰竭、肾结石）；血液系统疾病（贫血）；免疫系统疾病及其他（严重感染、痛风、抑郁、精神疾病、慢性疲劳综合征、纤维肌痛症、食物过敏、肿瘤等）。 2.既往有输血史、手术史及外伤史。 3.心电图异常。 4.妊娠或哺乳期妇女。 5.本研究期间，受试者已入选或计划入选另一项临床药物或装置/干预性研究。

Exclusion criteria：

Exclusion criteria for the case group Head CT or MRI examination shows intracranial hemorrhagic diseases (such as hemorrhagic stroke, subarachnoid hemorrhage, intracranial hematoma, epidural hematoma). 2. There were previous symptoms of neurological deficits, and the modified Rankin score (mRS) was >=2 points. 3. Patients with severe functional disorders of vital organs such as the heart, liver and kidneys. 4. Patients with malignant tumors, hematological diseases, immune system diseases, tuberculosis or moderate to severe infections. 5. There is a history of blood transfusion, surgery or trauma in the past. 6. Patients with abnormal electrocardiograms. 7. Pregnant or lactating women. 8.During this study period, the patient has been enrolled or is planned to be enrolled in another clinical drug or device/intervention study. Exclusion criteria for the case control group: Head CT or MRI examination shows intracranial hemorrhagic diseases (such as hemorrhagic stroke, subarachnoid hemorrhage, intracranial hematoma, epidural hematoma). 2. There were previous symptoms of neurological deficits, and the modified Rankin score (mRS) was >=2 points. 3. Patients with severe functional disorders of vital organs such as the heart, liver and kidneys. 4. Patients with malignant tumors, hematological diseases, immune system diseases, tuberculosis or moderate to severe infections. 5. There is a history of blood transfusion, surgery or trauma in the past. 6. Patients with abnormal electrocardiograms. 7. Patients undergoing intravenous thrombolysis and endovascular interventional therapy. 8. Pregnant or lactating women. 9.During this study period, the patient has been enrolled or is planned to be enrolled in another clinical drug or device/intervention study. Exclusion criteria for the healthy control group: 1. Other diseases exist: neurological diseases (cerebral infarction, cerebral hemorrhage, multiple sclerosis, etc.); All kinds of acute and chronic digestive system diseases; Circulatory system diseases (coronary heart disease, heart failure, atrial fibrillation); Respiratory system diseases (chronic obstructive pulmonary disease, chronic bronchitis, asthma); Metabolic diseases (obesity, hyperlipidemia, diabetes, metabolic syndrome, osteoporosis); Urinary system diseases (chronic kidney disease, renal failure, kidney stones); Blood system diseases (anemia); Immune system diseases and others (severe infections, gout, depression, mental illness, chronic fatigue syndrome, fibromyalgia, food allergies, tumors, etc.). 2. There is a history of blood transfusion, surgery and trauma in the past. 3. Abnormal electrocardiogram. 4. Pregnant or lactating women. 5.During this study period, the subjects have been enrolled or are planned to be enrolled in another clinical drug or device/intervention study.

研究实施时间：

Study execute time：

从 From 2025-11-01 00:00:00至 To 2026-03-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2025-11-01 00:00:00 至 To 2026-03-31 00:00:00

干预措施：

Interventions：

组别：	健康对照组	样本量：	100
Group：	Healthy Control Group	Sample size：	100
干预措施：	无	干预措施代码：
Intervention：	None	Intervention code：

组别：	病例组	样本量：	100
Group：	Case Group	Sample size：	100
干预措施：	无	干预措施代码：
Intervention：	None	Intervention code：

组别：	病例对照组	样本量：	100
Group：	Case Control Group	Sample size：	100
干预措施：	无	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)：	河北	市(区县)：	石家庄
Country：	China	Province：	Hebei	City：	Shijiazhuang
单位(医院)：	河北医科大学第二医院	单位级别：	三甲
Institution hospital：	The Second Hospital of Hebei Medical University	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	调节性T细胞	指标类型：	主要指标
Outcome：	Regulatory T cell	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	HMGB1	指标类型：	主要指标
Outcome：	High Mobility Group Box 1	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	MMP9	指标类型：	主要指标
Outcome：	Matrix metallopeptidase 9	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	TGF-β1	指标类型：	主要指标
Outcome：	Transforming growth factor-β	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	IL-10	指标类型：	主要指标
Outcome：	Interleukin 10	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：	血液	组织：
Sample Name：	Blood	Tissue：
人体标本去向	使用后销毁	说明
Fate of sample：	Destruction 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	岁 years
最大 Max age	80	岁 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）：

无

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：	无
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）：	研究结束后，通过ResMan(www.medresman.org.cn)方式共享
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	After the end of the study, it was shared by ResMan (www.medresman.org.cn).
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：	CRF;EDC
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	CRF;EDC
数据与安全监察委员会： Data and Safety Monitoring Committee：	有/Yes
注册人： Name of Registration：	2025-11-06 19:09:02