汉黄芩素促进自身免疫性肝炎模型大鼠Th17/Treg细胞平衡

doi:10.16352/j.issn.1001-6325.2024.01.0077

基础医学与临床 ›› 2024, Vol. 44 ›› Issue (1): 77-83.doi: 10.16352/j.issn.1001-6325.2024.01.0077

汉黄芩素促进自身免疫性肝炎模型大鼠Th17/Treg细胞平衡

邓娟, 王秀芳, 孙瑞青^*

空军军医大学第一附属医院消化内科,陕西西安 710032

收稿日期:2023-03-22 修回日期:2023-07-18 出版日期:2024-01-05 发布日期:2023-12-25
通讯作者: ^*:qwwmww@163.com

Wogonin promotes Th17/Treg cell balance in rat models with autoimmune hepatitis

DENG Juan, WANG Xiufang, SUN Ruiqing^*

Department of Gastroenterology, the First Affiliated Hospital of Air Force Medical University, Xi'an 710032, China

Received:2023-03-22 Revised:2023-07-18 Online:2024-01-05 Published:2023-12-25
Contact: ^*:qwwmww@163.com

摘要/Abstract

摘要： 目的探讨汉黄芩素(WG)对自身免疫性肝炎(AIH)大鼠Th17/Treg细胞平衡的影响。方法随机选出10只大鼠作为对照组,其余大鼠通过尾静脉注射伴刀豆球蛋白A(ConA,12.5 mg/kg)溶液构建AIH模型大鼠。将造模成功大鼠随机平分为AIH组、L-WG组(10 mg/kg)、M-WG组(20 mg/kg)、H-WG组(30 mg/kg)、H-WG+VPA组[30 mg/kg WG+300 mg/kg Notch信号通路激活剂丙戊酸(VPA)],每组10只,每天给药1次,持续10 d。ELISA检测血清中炎性因子及肝功能指标;HE染色观察肝脏组织病理形态;流式细胞测量术检测脾脏Th17/Treg细胞水平;Western blot检测脾脏类视黄酸相关孤儿受体γt(RORγt)、叉头框蛋白P3(Foxp3)以及肝组织Notch信号通路蛋白质的表达。结果对照组大鼠肝组织结构正常,染色清晰;AIH组大鼠肝组织细胞出现水肿,细胞体积增大导致肝窦受压变窄,出现大量炎性细胞浸润以及少量坏死现象。AIH组较对照组丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)活性、白介素(IL)-17和IL-23含量、Th17细胞水平、Th17/Treg、RORγt、Notch、hes家族bHLH转录因子1(HES1)、含YRPW基序的bHLH转录因子hes相关家族1(HEY1)蛋白表达均显著上升(P＜0.05),IL-10和TNF-β含量、Treg细胞水平、Foxp3蛋白水平均显著下降(P＜0.05);与AIH组相比,L-WG组、M-WG组、H-WG组肝损伤情况得到改善,ALT、AST活性、IL-17和IL-23含量、Th17细胞水平、Th17/Treg、RORγt、Notch、HES1、HEY1蛋白表达均显著降低(P＜0.05),IL-10和TNF-β含量、Treg细胞水平、Foxp3蛋白水平均显著升高(P＜0.05);VPA逆转了H-WG对AIH大鼠的改善效果。结论 WG可能通过下调Notch信号通路促进AIH大鼠Th17/Treg细胞平衡。

关键词: 汉黄芩素, Notch信号通路, 自身免疫性肝炎, Th17/Treg细胞

Abstract: Objective To investigate the impacts of wogonin (WG) on Th17/Treg cell balance in autoimmune hepatitis (AIH) rats. Methods A total of 10 rats were randomly selected as the control group. The remaining rats were injected with concanavalin A (ConA, 12.5 mg/kg) solution via tail vein to construct AIH model rat, which were randomly divided into AIH group, L-WG group (10 mg/kg), M-WG group (20 mg/kg), H-WG group (30 mg/kg), H-WG+VPA group (30 mg/kg WG+300 mg/kg Notch signal pathway activator VPA), 10 rats in each group and administered once a day for 10 days. Serum inflammatory factors and liver function indexes were detected by ELISA; HE staining was used to observe the pathological morphology of liver tissue; the level of spleen Th17/Treg cells was detected by flow cytometry; Western blot was used to detect the expression of spleen retinoid acid related orphan receptor γ t (RORγt), fork head box protein P3 (Foxp3) and liver Notch signal pathway proteins. Results The liver tissue structure of control group was normal and the staining was clear; In AIH group, the cells of liver tissue showed edema, the increase of cell volume led to the compression and narrowing of liver sinuses, and a large number of inflammatory cell infiltration and a small amount of necrosis occurred. The contents of alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin (IL)-17 and IL-23, level of Th17 cells, Th17/Treg, the expression of RORγt, Notch, hes family bHLH transcription factor 1 gene (HES1) and hes related family bHLH transcription factor with YRPW motif 1 (HEY1) protein in AIH group were greatly higher than those in control group (P＜0.05), the contents of IL-10 and TNF-β, level of Treg cells, and level of Foxp3 protein were greatly lower(P＜0.05); Compared with AIH group, the liver injury in L-WG group, M-WG group and H-WG group was improved, the contents of ALT, AST, IL-17 and IL-23, level of Th17 cells, Th17/Treg, the expression of RORγt, Notch, HES1 and HEY1 protein were greatly lower (P＜0.05), the contents of IL-10 and TNF-β, level of Treg cells, and level of Foxp3 protein were greatly higher (P＜0.05); VPA reversed the improvement effect of H-WG on AIH rats. Conclusions WG could promote Th17/Treg cell balance in AIH rats by down-regulating Notch signal pathway.

Key words: wogonin, Notch signal pathway, autoimmune hepatitis, Th17/Treg cell

中图分类号:

R285.5

邓娟, 王秀芳, 孙瑞青. 汉黄芩素促进自身免疫性肝炎模型大鼠Th17/Treg细胞平衡[J]. 基础医学与临床, 2024, 44(1): 77-83.

DENG Juan, WANG Xiufang, SUN Ruiqing. Wogonin promotes Th17/Treg cell balance in rat models with autoimmune hepatitis[J]. Basic & Clinical Medicine, 2024, 44(1): 77-83.

参考文献 19

[1]	Pape S, Schramm C, Gevers TJ. Clinical management of autoimmune hepatitis[J]. United European Gastroenterol J, 2019, 7:1156-1163.
[2]	Zhao Q, Yang J, Cui MY, et al. The reference genome sequence of scutellaria baicalensis provides insights into the evolution of wogonin biosynthesis[J]. Mol Plant, 2019, 12:935-950.
[3]	Chen C, Guo D, Lu G. Wogonin protects human retinal pigment epithelium cells from LPS-induced barrier dysfunction and inflammatory responses by regulating the TLR4/NF-κB signaling pathway[J]. Mol Med Rep, 2017, 15:2289-2295.
[4]	Chen J, Liu J, Wang Y, et al. Wogonin mitigates nonalcoholic fatty liver disease via enhancing PPARα/AdipoR2, in vivo and in vitro[J]. Biomed Pharmacother, 2017, 91:621-631.
[5]	Yamada Y, Saito H, Araki M, et al. Wogonin, a compound in scutellaria baicalensis, activates ATF4-FGF21 signaling in mouse hepatocyte AML12 cells[J]. Nutrients, 2022, 14:3920-3931.
[6]	Dai JM, Guo WN, Tan YZ, et al. Wogonin alleviates liver injury in sepsis through Nrf2-mediated NF-κB signalling suppression[J]. J Cell Mol Med, 2021, 25:5782-5798.
[7]	高丽萍,毛小荣.辅助性T细胞17/调节性T细胞失衡在大鼠自身免疫性肝炎模型中的研究[J].中国临床药理学杂志,2020,36:3021-3025.
[8]	Luiken S, Fraas A, Bieg M, et al. Notchtarget gene HES5 mediates oncogenic and tumor suppressive functions in hepatocarcinogenesis[J]. Oncogene, 2020, 39:3128-3144.
[9]	Shi J, Han G, Wang J, et al. Matrine promotes hepatic oval cells differentiation into hepatocytes and alleviates liver injury by suppression of Notch signalling pathway[J]. Life Sci, 2020, 261:118354. doi: 10.1016/j.lfs.2020.118354.
[10]	Liu J, Liu S, Pan W, et al. Wogonoside attenuates the articular cartilage injury and the infiltration of Th1/Th2-type cytokines in papain-induced osteoarthritis in rat model via inhibiting the NF-κB and ERK1/2 activation[J]. Immunopharmacol Immunotoxicol, 2021, 43:343-352.
[11]	Méndez A, Rojas DA, Ponce CA, et al. Primary infection by Pneumocystis induces Notch-independent Clara cell mucin production in rat distal airways[J]. PLoS One, 2019, 14:e0217684. doi: 10.1371/journal.pone.0217684.
[12]	Assis DN. Immunopathogenesis of autoimmune hepatitis[J]. Clin Liver Dis (Hoboken), 2020, 15:129-132.
[13]	Du XS, Li HD, Yang XJ, et al. Wogonin attenuates liver fibrosis via regulating hepatic stellate cell activation and apoptosis[J]. Int Immunopharmacol, 2019, 75:105671. doi: 10.1016/j.intimp.2019.05.056.
[14]	Fu T, Chen Y, Li J, et al. Exploring the effective components and mechanism of action of japanese ardisia in the treatment of autoimmune hepatitis based on network pharmacology and experimental verification[J]. Pharmaceuticals (Basel), 2022, 15:1457-1473.
[15]	Lee GR. The balance of Th17 versus Treg cells in autoimmunity[J]. Int J Mol Sci, 2018, 19:730-743.
[16]	Duan JL, Ruan B, Yan XC, et al. Endothelial Notch activation reshapes the angiocrine of sinusoidal endothelia to aggravate liver fibrosis and blunt regeneration in mice[J]. Hepatology, 2018, 68:677-690.
[17]	Xu Z, Huang L, Zhang T, et al. Shikonin inhibits the proliferation of cervical cancer cells via FAK/AKT/GSK3β signalling[J]. Oncol Lett, 2022, 24:304-313.
[18]	Yin X, Wei H, Wu S, et al. DAPT reverses the Th17/Treg imbalance in experimental autoimmune uveitis in vitro via inhibiting Notch signaling pathway[J]. Int Immunopharmacol, 2020, 79:106107. doi: 10.1016/j.intimp.2019.106107.
[19]	冯锦.miR-20b介导的Notch信号通路对自身免疫性肝炎模型小鼠巨噬细胞的免疫调节及机制的研究[J].免疫学杂志,2022,38:378-385.

汉黄芩素促进自身免疫性肝炎模型大鼠Th17/Treg细胞平衡

Wogonin promotes Th17/Treg cell balance in rat models with autoimmune hepatitis

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