黄芩苷调控炎性因子治疗肠道急性移植物抗宿主病的研究

曹慧琴; 韦玮; 崔兴

doi:10.3969/j.issn.1006-2157.2024.09.011

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黄芩苷调控炎性因子治疗肠道急性移植物抗宿主病的研究

实验研究 | 更新时间：2024-10-09

- 黄芩苷调控炎性因子治疗肠道急性移植物抗宿主病的研究
- Study on baicalin alleviating the symptoms of intestinal acute graft versus host disease by inhibiting inflammatory factors
- 北京中医药大学学报 2024年47卷第9期页码：1272-1281
- 作者机构：
  
  1.延安大学附属医院血液科　延安　716000
  2.延安大学附属医院神经外科
  3.山东中医药大学第二附属医院肿瘤中心
- 作者简介：
  
  曹慧琴，女，在读博士生，副主任医师
  #崔兴，男，教授，主任医师，博士生导师，主要研究方向：中西医结合治疗肿瘤、血液病的临床及实验研究，E-mail: cdz45@163.com
- 基金信息：
  
  国家自然科学基金面上项目(81774080);泰山学者青年专家人才项目(tsqn201812145)
- DOI：10.3969/j.issn.1006-2157.2024.09.011
  中图分类号： R285.5
- 纸质出版日期：2024-09-30，
  
  网络出版日期：2024-08-14，
  
  收稿日期：2024-03-19，
- 稿件说明：
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曹慧琴, 韦玮, 崔兴. 黄芩苷调控炎性因子治疗肠道急性移植物抗宿主病的研究[J]. 北京中医药大学学报, 2024,47(9):1272-1281.

CAO Huiqin, WEI Wei, CUI Xing. Study on baicalin alleviating the symptoms of intestinal acute graft versus host disease by inhibiting inflammatory factors[J]. Journal of Beijing University of Traditional Chinese Medicine, 2024,47(9):1272-1281.
曹慧琴, 韦玮, 崔兴. 黄芩苷调控炎性因子治疗肠道急性移植物抗宿主病的研究[J]. 北京中医药大学学报, 2024,47(9):1272-1281. DOI： 10.3969/j.issn.1006-2157.2024.09.011.

CAO Huiqin, WEI Wei, CUI Xing. Study on baicalin alleviating the symptoms of intestinal acute graft versus host disease by inhibiting inflammatory factors[J]. Journal of Beijing University of Traditional Chinese Medicine, 2024,47(9):1272-1281. DOI： 10.3969/j.issn.1006-2157.2024.09.011.

摘要

目的

探讨黄芩苷干预肠道急性移植物抗宿主病(acute graft versus host disease，aGVHD)的作用机制。

方法

分离采集健康志愿者和肠道aGVHD患者的外周血单个核细胞，富集分析其测序得到的差异mRNA，取差异mRNA与黄芩苷作用靶点的交集并进行分析。制备SPF级BALB/c H-2 d雄性小鼠的单核细胞悬液(1×10

骨髓细胞＋ 1×10

脾细胞)，将其通过尾静脉输入4 h内照射了

Co-X射线的SPF级CB6F1雌性小鼠，造模后小鼠随意分为模型组、黄芩苷组。另取6只CB6F1雌性小鼠作为正常组。造模后黄芩苷组给予30 mg/(kg·d)黄芩苷灌胃，模型组与正常组予等容量的生理盐水灌胃，连续14 d，每日观察小鼠生存状况。干预结束，检测小鼠血清细胞因子，进行小鼠肠道aGVHD相对评分、小肠黏膜病理炎症评分，小肠组织免疫组化、免疫荧光检测肿瘤坏死因子-α(TNF-α)、白细胞介素-2(IL-2)表达。

结果

筛选到健康志愿者与肠道aGVHD患者差异mRNA共2 131个，KEGG分析发现集中在肿瘤坏死因子等通路上。分析差异基因与黄芩苷作用靶点交集，发现TNF-α、IL-2是黄芩苷治疗肠道aGVHD的核心靶点。小鼠aGVHD模型研究发现，经过黄芩苷治疗后，与模型组比较，黄芩苷组aGVHD相对评分、小肠黏膜病理炎症相对评分降低，血清TNF-α、IL-2下降，小肠免疫组化及免疫荧光检测的TNF-α、IL-2表达均降低，均

0.05。

结论

黄芩苷能够抑制血清和小肠黏膜TNF-α、IL-2的水平和浸润，降低移植后肠道aGVHD的发病率。

Abstract

Objective

To explore the mechanism of baicalin intervention in gastrointestinal acute graft versus host disease (aGVHD).

Methods

Peripheral blood mononuclear cells from patients with intestinal aGVHD and healthy volunteers were collected for high-throughput sequencing and differential mRNA enrichment analysis. The intersection of the baicalin target and differential mRNA was analyzed. CB6F1 mice were irradiated with

Co X-rays. After irradiation

a mononuclear cell suspension (1×10

bone marrow cell + 1×10

spleen cell) of BALB/cH-2 d mice was injected into CB6F1 mice through the tail vein

and these mice were randomly devided into the model group and the baicalin group. 6 SPF female mice were selected as the normal group. After modeling

the baicalin group was administered 30 mg/(kg·d) of baicalin by gavage

and the model and normal groups were gavaged with normal saline of equal volume. Serum cytokines were detected after 14 days

and aGVHD scores and small intestinal mucosa pathdogy scores

immunohistochemical

and immunofluorescence detection were performed.

Results

A total of 2

131 different mRNAs were identified from patients with intestinal aGVHD and healthy volunteers. Kyoto Encyclopedia of Genes and Genomes analysis indicated that these mRNAs enriched the TNF signaling pathway and other pathways. The baicalin target was intersected with the above differential genes

and TNF-α and IL-2 were the primary baicalin targets in the treatment of intestinal aGVHD. The aGVHD scores and small intestinal mucosal pathology scores after baicalin treatment were significantly better than those in the model group

serum TNF-α and IL-2 levels were significantly decreased

and the TNF-α and IL-2 protein expression levels in intestinal immunohistochemistry and immunofluorescence were also significantly recovered (

0.05).

Conclusion

Baicalin can reduce the inflammatory infiltration and destruction of intestinal mucosa by reducing TNF-α and IL-2 production and reducing the incidence of intestinal aGVHD after transplantation.

关键词

黄芩苷急性移植物抗宿主病肿瘤坏死因子-α白细胞介素-2肠黏膜网络药理学小鼠

Keywords

baicalinacute graft versus host diseasetumor necrosis factor-αinterleukin-2intestinal mucosanetwork pharmacologymice

references

黄晓军，吴德沛，刘代红，等. 实用造血干细胞移植[M]. 北京：人民卫生出版社，2014: 246－247.

MURPHY WJ, WELNIAK LA, TAUB DD, et al. Differential effects of the absence of interferon-gamma and IL-4 in acute graft-versus-host disease after allogeneic bone marrow transplantation in mice[J]. J Clin Invest, 1998, 102(9): 1742－1748.

王书红，达万明，靳海杰，等. 急性移植物抗宿主病病人血清IL-2、IL-8、IL-10及TNF-α水平变化的研究[J]. 中国实验血液学杂志，2006, 14(4): 755－758.

GAO Q, ZHANG WJ, ZHANG D, et al. Can cytokine detection predict the occurrence and outcome of aGVHD after allo-HCT? A retrospective study[J]. Discov Med, 2023, 35(176): 242－250.

QI L, PENG J, HUANG X, et al. Longitudinal dynamics of gut microbiota in the pathogenesis of acute graft-versus-host disease[J]. Cancer Med, 2023, 12(24): 21567－21578.

KOVALENKO I, SALEEM T, SHAH M, et al. Novel pharmacological treatment options of steroid-refractory graft-versus-host disease[J]. Adv Hematol, 2023, 2023: 9949961.

李天如，张颖，谈宁. 黄芩苷减轻小鼠结肠炎损伤的机制研究[J]. 解剖科学进展，2022, 28(5): 577－580.

CUI L, FENG L, ZHANG ZH, et al. The anti-inflammation effect of baicalin on experimental colitis through inhibiting TLR4/NF－κB pathway activation[J]. Int Immunopharmacol, 2014, 23(1): 294－303.

肖敏，徐洪来，吴栋杰，等. 黄芩苷对泛发性脓疱型银屑病患者机体Th1/Th2失衡及T-bet/GAGA－3表达的影响[J]. 广西医学，2021, 43(16): 1972－1976.

陈慧瑶，张伟，方芳，等. 肠三叶因子通过自噬在急性移植物抗宿主病中发挥保护作用[J]. 温州医科大学学报，2017, 47(7): 480－484.

杨志刚，曾耀英，王青，等. 小鼠异基因骨髓移植急性移植物抗宿主病模型的建立[J]. 中国病理生理杂志，2004, 20(10): 1947－ 1949.

GHIMIRE S, WEBER D, MAVIN E, et al. Pathophysiology of GvHD and other HSCT-related major complications[J]. Front Immunol, 2017, 8: 79.

QIAN L, SHEN JL. Hydrogen therapy may be an effective and specific novel treatment for acute graft-versus-host disease (GVHD)[J]. J Cell Mol Med, 2013, 17(8): 1059－1063.

MAMMADLI M, HARRIS R, SUO LY, et al. Interleukin－2－inducible T-cell kinase (Itk) signaling regulates potent noncanonical regulatory T cells[J]. Clin Transl Med, 2021, 11(12): e625.

DUKAT-MAZUREK A, BIENIASZEWSKA M, HELLMANN A, et al. Association of cytokine gene polymorphisms with the complications of allogeneic haematopoietic stem cell transplantation[J]. Hum Immunol, 2017, 78(11/12): 672－683.

LI X, CHEN T, GAO Q, et al. A panel of 4 biomarkers for the early diagnosis and therapeutic efficacy of aGVHD[J]. JCI Insight, 2019, 4(16): e130413.

JUNG SH, KANG KD, JI D, et al. The flavonoid baicalin counteracts ischemic and oxidative insults to retinal cells and lipid peroxidation to brain membranes[J]. Neurochem Int, 2008, 53(6/7/8): 325－337.

朱磊，沈洪，顾培青，等. 黄芩苷对溃疡性结肠炎模型大鼠炎性反应、凋亡的影响及与PI3K/AKT通路的关系[J]. 中华中医药杂志，2017, 32(9): 4001－4004.

朱磊，沈洪，顾培青，等. 黄芩苷对溃疡性结肠炎模型大鼠NF－κB表达的影响[J]. 南京中医药大学学报，2016, 32(5): 447－450.

张霞，杜文泽，赵汉清，等. 汉黄芩苷对溃疡性结肠炎大鼠促炎因子、氧化应激标志物水平的影响及黏膜修复作用[J]. 中国老年学杂志，2022, 42(12): 2994－2998.

YAN YG, LI LH, WU KN, et al. A combination of baicalin and berberine hydrochloride ameliorates dextran sulfate sodium-induced colitis by modulating colon gut microbiota[J]. J Med Food, 2022, 25(8): 853－862.

CHOU TC, CHANG LP, LI CY, et al. The antiinflammatory and analgesic effects of baicalin in carrageenan-evoked thermal hyperalgesia[J]. Anesth Analg, 2003, 97(6): 1724－1729.

于丰彦，黄绍刚，张海燕，等. 黄芩苷对溃疡性结肠炎患者信号转导和转录激活因子表达的影响[J]. 中国中西医结合杂志，2015, 35(4): 419－424.

邹颖，迟宏罡，欧阳霖芮，等. 黄芩苷对实验性结肠炎小鼠TLRs/MyD88通路的作用研究[J]. 天然产物研究与开发，2014, 26(6): 952－956.

黄梅，颜景颖. 基于NF－κB/COX－2信号通路探讨芍药内酯苷对溃疡性结肠炎模型大鼠的影响[J]. 中医学报，2022, 37(2): 365－370.

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