吴茱萸次碱通过抑制TNFR-MAPK/NF-κB及NLRP3炎症小体信号通路减轻MSU晶体诱导的痛风性炎症题目：血府逐瘀汤调控腺苷改善急性脑损伤大鼠的血脑屏障完整性。

WANG Yang; YAN Qiu-ju; HU En; WU Yao; DING Ruo-qi; CHEN Quan; CHENG Meng-han; YANG Xi-ya; TANG Tao; TANG Tao; LI Teng

doi:10.1007/s11655-025-4200-7

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吴茱萸次碱通过抑制TNFR-MAPK/NF-κB及NLRP3炎症小体信号通路减轻MSU晶体诱导的痛风性炎症题目：血府逐瘀汤调控腺苷改善急性脑损伤大鼠的血脑屏障完整性。

Original Article | Updated：2025-07-11

- 吴茱萸次碱通过抑制TNFR-MAPK/NF-κB及NLRP3炎症小体信号通路减轻MSU晶体诱导的痛风性炎症题目：血府逐瘀汤调控腺苷改善急性脑损伤大鼠的血脑屏障完整性。
- Xuefu Zhuyu Decoction Improves Blood-Brain Barrier Integrity in Acute Traumatic Brain Injury Rats via Regulating Adenosine^*
- 中国结合医学杂志（英文版） 2025年31卷第7期页码：624-634
- Affiliations：
  
  1.Institute of Integrative Medicine, Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha (410008), China
  2.NATCM Key Laboratory of TCM Gan, Xiangya Hospital, Central South University, Changsha (410008), China
  3.National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha (410008), China
  4.Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Jiangxi, Nanchang (330004), China
- Author bio：
  
  Dr. LI Teng, E-mail: litengxiangya@csu.edu.cn
- Funds：
  
  the China Postdoctoral Science Foundation(2024M753699);the National Natural Science Foundation of China(82274371);Natural Science Foundation of Changsha(kq2403042);Natural Science Foundation of Hunan Province(2023JJ30944);Key Research and Development Program of Hunan Province(2023SK2021);the Fundamental Research Funds for the Central Universities of Central South University(1053320232786)
- DOI：10.1007/s11655-025-4200-7
  中图分类号：
- 录用日期：2024-08-12，
  
  网络出版日期：2025-01-08，
  
  纸质出版日期：2025-07
- Accepted：
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吴茱萸次碱通过抑制TNFR-MAPK/NF-κB及NLRP3炎症小体信号通路减轻MSU晶体诱导的痛风性炎症题目：血府逐瘀汤调控腺苷改善急性脑损伤大鼠的血脑屏障完整性。[J]. 中国结合医学杂志（英文版）, 2025,31(7):624-634.

WANG Yang, YAN Qiu-ju, HU En, et al. Xuefu Zhuyu Decoction Improves Blood-Brain Barrier Integrity in Acute Traumatic Brain Injury Rats via Regulating Adenosine^*[J]. Chinese journal of integrative medicine, 2025, 31(7): 624-634.
吴茱萸次碱通过抑制TNFR-MAPK/NF-κB及NLRP3炎症小体信号通路减轻MSU晶体诱导的痛风性炎症题目：血府逐瘀汤调控腺苷改善急性脑损伤大鼠的血脑屏障完整性。[J]. 中国结合医学杂志（英文版）, 2025,31(7):624-634. DOI： 10.1007/s11655-025-4200-7.

WANG Yang, YAN Qiu-ju, HU En, et al. Xuefu Zhuyu Decoction Improves Blood-Brain Barrier Integrity in Acute Traumatic Brain Injury Rats via Regulating Adenosine^*[J]. Chinese journal of integrative medicine, 2025, 31(7): 624-634. DOI： 10.1007/s11655-025-4200-7.

摘要

目的:

基于体内实验和代谢组学实验

探索血府逐瘀汤(XFZYD)的神经保护作用.

方法:

将30只大鼠随机分为3组

采用控制性皮质撞击模型(CCI)模拟创伤性脑损伤(TBI)

并分为三组:假手术组、CCI组和XFZYD组. 采用口服给药方式

连续给药3天. 随后进行神经系统功能测试、组织学染色、凝血和血液流变学测定

以及Western Blot分析. 非靶向代谢组学用来鉴定代谢产物. 通过酶联免疫吸附测定和免疫荧光法验证了关键代谢物.

结果:

XFZY

D显著缓解CCI模型大鼠的神经功能障碍(

0.01)

但对凝血功能无影响. 伊文思蓝和lgG染色结果表明

XFZYD有效减轻了血脑屏障 (BBB) 的破坏(

0.05

0.01). 此外

XFZYD血府逐瘀汤不仅增加了胶原IV、胶原蛋白和胶原闭合带1的表达

还降低了基质金属蛋白酶-9(MMP-9)和环氧合酶-2(COX-2)的表达

保护了BBB的完整性(均

0.05). 代谢组学鉴定出了9个潜在的代谢物

所有这些代谢物都可通过在XFZYD治疗后被逆转. 腺苷是与BBB修复关系最为密切的显著变化代谢物. XFZYD显著降低了平衡核苷转运蛋白2(ENT2)的水平

并增加了腺苷的浓度(

0.01)

这可能有助于提高BBB的完整性.

结论:

XFZYD通过降低MMP-9和COX-2的水平

改善了TBI后的BBB损伤. 通过进一步的代谢组学研究

我们发现XFZYD可能通过调控腺苷代谢

经由ENT2途径

对BBB发挥保护作用.

Abstract

Objective:

To explore the neuroprotective effects of Xuefu Zhuyu Decoction (XFZYD) based on

in vivo

and metabolomics experiments.

Methods:

Traumatic brain injury (TBI) was induced via a controlled cortical impact (CCI) method. Thirty rats were randomly divided into 3 groups (10 for each): sham

CCI and XFZYD groups (9 g/kg). The administration was performed by intragastric administration for 3 days. Neurological functions tests

histology staining

coagulation and haemorheology assays

and Western blot were examined. Untargeted metabolomics was employed to identify metabolites. The key metabolite was validated by enzyme-linked immunosorbent assay and immunofluorescence.

Results:

XFZYD significantly alleviated neurological dysfunction in CCI model rats (

0.01) but had no impact on coagulation function. As evidenced by Evans blue and IgG staining

XFZYD effectively prevented blood-brain barrier (BBB) disruption (

0.05

0.01). Moreover

XFZYD not only increased the expression of collagen Ⅳ

occludin and zona occludens 1 but also decreased matrix metalloproteinase-9 (MMP-9) and cyclooxygenase-2 (COX-2)

which protected BBB integrity (all

0.05). Nine potential metabolites were identified

and all of them were reversed by XFZYD. Adenosine was the most significantly altered metabolite related to BBB repair. XFZYD significantly reduced the level of equilibrative nucleoside transporter 2 (ENT2) and increased adenosine (

0.01)

which may improve BBB integrity.

Conclusions:

XFZYD ameliorates BBB disruption after TBI by decreasing the levels of MMP-9 and COX-2. Through further exploration via metabolomics

we found that XFZYD may exert a protective effect on BBB by regulating adenosine metabolism via ENT2.

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