Effect of <italic style="font-style: italic">Fugan Huaxian Decoction </italic>（扶肝化纤汤） on Th17/Treg Balance and Related Transcription Factors in Hepatic Fibrosis with Healthy <italic style="font-style: italic">Qi</italic> Deficiency and Toxin Accumulation Pattern Model Rats

ZHONG Yan; TAN Qianren; CUI Junsong; LI Qing; LU Luxing; XIAO Zhenghua

doi:10.13288/j.11-2166/r.2023.19.013

您当前的位置：

首页 >

文章列表页 >

Effect of Fugan Huaxian Decoction （扶肝化纤汤） on Th17/Treg Balance and Related Transcription Factors in Hepatic Fibrosis with Healthy Qi Deficiency and Toxin Accumulation Pattern Model Rats

更新时间：2023-09-26

- Effect of Fugan Huaxian Decoction （扶肝化纤汤） on Th17/Treg Balance and Related Transcription Factors in Hepatic Fibrosis with Healthy Qi Deficiency and Toxin Accumulation Pattern Model Rats
- Journal of Traditional Chinese Medicine Vol. 64, Issue 19, Pages: 2019-2026(2023)
- 作者机构：
  
  1.贵州中医药大学，贵州省贵阳市南明区市东路50号，550005
  2.贵州中医药大学第二附属医院
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2023.19.013
  CLC：
- Received：02 June 2023，
  
  Revised：2023-07-05，
  
  Published：02 October 2023
- 稿件说明：
移动端阅览
钟燕,谭芊任,崔峻松等.扶肝化纤汤对肝纤维化正虚毒蕴血瘀证模型大鼠Th17/Treg平衡及相关转录因子的影响[J].中医杂志,2023,64(19):2019-2026.

ZHONG Yan,TAN Qianren,CUI Junsong,et al.Effect of Fugan Huaxian Decoction （扶肝化纤汤） on Th17/Treg Balance and Related Transcription Factors in Hepatic Fibrosis with Healthy Qi Deficiency and Toxin Accumulation Pattern Model Rats[J].Journal of Traditional Chinese Medicine,2023,64(19):2019-2026.
钟燕,谭芊任,崔峻松等.扶肝化纤汤对肝纤维化正虚毒蕴血瘀证模型大鼠Th17/Treg平衡及相关转录因子的影响[J].中医杂志,2023,64(19):2019-2026. DOI： 10.13288/j.11-2166/r.2023.19.013.

ZHONG Yan,TAN Qianren,CUI Junsong,et al.Effect of Fugan Huaxian Decoction （扶肝化纤汤） on Th17/Treg Balance and Related Transcription Factors in Hepatic Fibrosis with Healthy Qi Deficiency and Toxin Accumulation Pattern Model Rats[J].Journal of Traditional Chinese Medicine,2023,64(19):2019-2026. DOI： 10.13288/j.11-2166/r.2023.19.013.

摘要

目的

从免疫角度探讨扶肝化纤汤抗肝纤维化的可能作用机制。

方法

48只SD大鼠随机分为空白组、模型组、秋水仙碱组及扶肝化纤汤高、中、低剂量组，每组8只。除空白组外，其余各组大鼠建立肝纤维化正虚毒蕴血瘀证大鼠病证结合模型，共6周。造模成功后，扶肝化纤汤高、中、低剂量组分别给予扶肝化纤汤颗粒37.50、18.75、9.38 g/（kg·d）灌胃，秋水仙碱组给予秋水仙碱片2 mg/（kg·d）灌胃，空白组与模型组给予纯净水10 ml/（kg·d）灌胃，连续干预3周。实验期间记录大鼠一般情况。干预结束后HE染色观察肝脏组织病理学形态；ELISA法检测血清中白细胞介素10（IL-10）、白细胞介素17（IL-17）含量；流式细胞术检测外周血中辅助性T细胞17（Th17）、调节性T细胞（Treg）表达，计算Th17/Treg值；qRT-PCR法检测肝脏组织中维甲酸相关核孤儿受体γ（RORγt）、叉状头/翅膀状螺旋转录因子（FoxP3）mRNA表达。

结果

与空白组比较，模型组大鼠一般情况为精神萎靡，活动减少、扎推，弓背喜卧，灌胃无抵抗，进食量明显减少，大便溏薄、肛门污秽，体质量增加缓慢，毛发枯燥无光泽，四肢皮肤青紫瘀斑变暗，尾部皮肤有不同程度紫黑斑；HE染色显示肝脏组织肝纤维化增生明显；血清IL-17、外周血Th17表达及Th17/Treg值、肝组织RORγt mRNA表达升高，IL-10、Treg表达、FoxP3 mRNA表达降低（

＜0.05或

＜0.01）。与模型组比较，各药物干预组大鼠一般情况及HE染色肝脏组织肝纤维化情况均有改善，扶肝化纤汤高、中剂量组及秋水仙碱组IL-17、Th17表达、Th17/Treg值、RORγt mRNA表达降低，IL-10、Treg表达、FoxP3 mRNA表达升高，扶肝化纤低剂量组IL-17、Th17表达、RORγt mRNA表达降低，IL-10、FoxP3 mRNA表达升高（

＜0.05或

＜0.01）；且扶肝化纤汤高剂量组各指标改善效果优于秋水仙碱组和扶肝化纤汤中、低剂量组（

＜0.05或

＜0.01）。

结论

扶肝化纤汤可能通过调节特异性转录因子FoxP3、RORγt表达，影响Th17、Treg细胞分化及Th17/Treg平衡，调节IL-10、IL-17分泌，进而调节免疫平衡发挥抗肝纤维化的作用。

Abstract

Objective

To investigate the possible mechanism of

Fugan Huaxian Decoction

（扶肝化纤汤， FHD） against hepatic fibrosis （HF） from the perspective of immunity.

Methods

Forty-eight SD rats were randomly divided into blank group， model group， colchicine group， FHD high-， medium- and low-dose group， with eight rats in each group. Except for the blank group， the disease-syndrome combined model of HF with healthy

deficiency and toxin accumulation pattern was established during six weeks in the other five groups. After successful modeling， the high-， medium- and low-dose FHD groups were respectively given 37.5， 18.75 and 9.38 g/（kg·d） of FHD granules by gavage， while the colchicine group received 2 mg/ （kg·d） of colchicine tablets by gavage， and the blank group and the model group were given 10 ml/（kg·d） of purified water， all for 3 weeks. The general condition of the rats was recorded. After the treatment， the histopathological morphology of the liver was observed by HE staining， and the levels of interleukin 10 （IL-10） and interleukin 17 （IL-17） in serum were determined by enzyme-linked immunosorbent assay （ELISA）. The expression of helper T cells 17 （Th17） and regulatory T cells （Treg） in peripheral blood were detected by flow cytometry， and the Th17/Treg value was calculated. The mRNA expression of retinoic acid-related nuclear orphan receptor γ （RORγt） and fork-head/wing-like helix transcription factor （FoxP3） in liver tissue were detected by qRT-PCR.

Results

Compared to the general condition of rats in the blank group， those in the model group were listless， less active， stretched and pushed， arched and prone， having no resistance to gavage， significantly reduced food intake， loose stools， dirty anus， slow weight gain， dry and dull hair， purple and darkening skin of the limbs with ecchymoses， purple and black spots with varying degrees of the skin of the tail； hepatic fibrosis and hyperplasia of rats in model group were more obvious； serum IL-17， peripheral blood Th17 expression and Th17/Treg value， RORγt mRNA expression in the liver tissue significantly increased in the model group， while expression of IL-10， Treg and FoxP3 mRNA significantly decreased （

＜0.05 or

＜0.01）. Compared to those in the model group， the general condition of the rats and the liver fibrosis of HE stained liver tissue were improved in all the medication groups； the expression of IL-17 and Th17， Th17/Treg， and RORγt mRNA expression significantly decreased， while expression of IL-10， Treg， and FoxP3 mRNA increased in the high- and medium-dose FHD groups and the colchicine group； the expression of IL-17， Th17， and RORγt mRNA decreased， while the expression of IL-10 and FoxP3 mRNA increased in the low-dose FHD group （

＜0.05 or

＜0.01）. And more improvements were found in the FHD high-dose group than FHD medium- and low-dose groups and colchicine group （

＜0.05 or

＜0.01）.

Conclusion

FHD can may regulate immune balance and act against fibrosis by regulating the expression of specific transcription factors FoxP3 and RORγt， affecting the differentiation of Th17 and Treg cells and Th17/Treg balance， and regulating the secretion of IL-10 and IL-17.

关键词

Keywords

references

FORNER A ， REIG M ， BRUIX J . Hepatocellular carcinoma ［J］. Lancet ， 2018 ， 391 （ 10127 ）： 1301 - 1314 .

CALIGIURI A ， GENTILINI A ， PASTORE M ， et al . Cellular and molecular mechanisms underlying liver fibrosis regression ［J］. Cells ， 2021 ， 10 （ 10 ）： 2759 .

朱璐璐，王汉裕，吕东勇，等 . 基于中医阴阳学说探讨巨噬细胞极化在肝纤维化中的作用［J］. 中医杂志， 2019 ， 60 （ 12 ）： 1025 - 1029 .

YANG F ， LI H ， LI Y ， et al . Crosstalk between hepatic stellate cells and surrounding cells in hepatic fibrosis ［J］. Int Immunopharmacol ， 2021 ， 99 ： 108051 . doi： 10.1016/j.intimp.2021.108051 http://dx.doi.org/10.1016/j.intimp.2021.108051 .

DRESCHER HK ， BARTSCH LM ， WEISKIRCHEN S ， et al . Intrahepatic Th17/Treg cells in homeostasis and disease：it's all about the balance ［J］. Front Pharmacol ， 2020 ， 11 ： 588436 . doi： 10.3389/fphar.2020.588436 http://dx.doi.org/10.3389/fphar.2020.588436 .

崔峻松，谭芊任，肖政华 . 扶肝化纤汤治疗慢性乙型病毒性肝炎肝纤维化临床研究［J］. 亚太传统医药， 2017 ， 13 （ 4 ）： 131 - 133 .

肖政华，杨辉，杨君，等 . 扶肝化纤汤对肝纤维化模型大鼠MAPK信号通路的影响［J］. 中草药， 2019 ， 50 （ 14 ）： 3374 - 3381 .

肖政华，邹艳，杨辉，等 . 扶肝化纤汤含药血清对TGF-β1诱导HSC-T6细胞增殖及TGF-β1/Smad信号通路的影响［J］. 中医杂志， 2019 ， 60 （ 19 ）： 1673 - 1678 .

程明亮，杨长青 . 肝纤维化的基础研究及临床［M］. 北京：人民卫生出版社， 2002 ： 20 .

周玉平 . 肝纤维化病证结合动物模型评析［J］. 时珍国医国药， 2011 ， 22 （ 6 ）： 1504 - 1505 .

徐珊，包剑锋，周敏，等 . 肝纤维化病证结合模型的研制［J］. 中国中医药科技， 2009 ， 16 （ 2 ）： 81 - 83，79 .

傅柳，严小军，尚广彬，等 . 肝纤维化病证结合动物模型的建立及评价方法研究进展［J］. 中华中医药杂志， 2022 ， 37 （ 6 ）： 3330 - 3334 .

陈奇 . 中药药理研究方法学［M］. 北京：人民卫生出版社， 2011 ： 1263 .

邹艳，陈贵赏，肖政华，等 . 浅析扶肝化纤汤的处方组成、药理作用及临床应用［J］. 当代医药论丛， 2017 ， 15 （ 22 ）： 204 - 206 .

LAN YT ， WANG ZL ， TIAN P ， et al . Treg/Th17 imbalance and its clinical significance in patients with hepatitis B-associated liver cirrhosis ［J］. Diagn Pathol ， 2019 ， 14 （ 1 ）： 114 .

ZHANG XW ， MI S ， LI Z ， et al . Antagonism of interleukin-17A ameliorates experimental hepatic fibrosis by restoring the IL-10/STAT3-suppressed autophagy in hepatocytes ［J］. Oncotarget ， 2017 ， 8 （ 6 ）： 9922 - 9934 .

TAN Z ， QIAN X ， JIANG R ， et al . IL-17A plays a critical role in the pathogenesis of liver fibrosis through hepatic stellate cell activation ［J］. J Immunol ， 2013 ， 191 （ 4 ）： 1835 - 1844 .

STEEN EH ， WANG X ， BALAJI S ， et al . The role of the anti-inflammatory cytokine interleukin-10 in tissue fibrosis ［J］. Adv Wound Care （New Rochelle）， 2020 ， 9 （ 4 ）： 184 - 198 .

HUANG YH ， CHEN MH ， GUO QL ， et al . Interleukin-10 promotes primary rat hepatic stellate cell senescence by upregulating the expression levels of p53 and p21 ［J］. Mol Med Rep ， 2018 ， 17 （ 4 ）： 5700 - 5707 .

章蓝月，陶春鹤，轩晨，等 . 益气化瘀柔肝方通过调控NLRP3炎性小体活性缓解CCl 4 诱导的大鼠肝纤维化［J］. 免疫学杂志， 2021 ， 37 （ 10 ）： 829 - 836，853 .

ZHENG JR ， WANG ZL ， FENG B . Hepatitis B functional cure and immune response ［J］. Front Immunol ， 2022 ， 13 ： 1075916 . doi： 10.3389/fimmu.2022.1075916 http://dx.doi.org/10.3389/fimmu.2022.1075916 .

冯锦，吴建红，熊响莲，等 . 紫杉醇通过调控JAK2/STAT3通路对肝纤维化模型大鼠Th17/Treg影响的研究［J］. 中国免疫学杂志， 2022 ， 38 （ 13 ）： 1564 - 1569 .

REN J ， LI B . The functional stability of FOXP3 and RORγt in Treg and Th17 and their therapeutic applications ［J］. Adv Protein Chem Struct Biol ， 2017 ， 107 ： 155 - 189 . doi： 10.1016/bs.apcsb.2016.10.002 http://dx.doi.org/10.1016/bs.apcsb.2016.10.002 .

KONOPACKI C ， PRITYKIN Y ， RUBTSOV Y ， et al . Transcription factor Foxp1 regulates Foxp3 chromatin binding and coordinates regulatory T cell function ［J］. Nat Immunol ， 2019 ， 20 （ 2 ）： 232 - 242 .

查看原文

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Immune-Metabolic Reprogramming in Hepatic Fibrosis and Its Micro-Level Syndrome Differentiation and Treatment：from the Perspective of "Liver Being the General and Spleen Being the Defender"

Effects of Jianpi Bushen Yiqi Decoction （健脾补肾益气方） on Splenic Th/Treg Immune Axis and the Neuromuscular Junction AChR in Muscle Groups in Experimental Autoimmune Myasthenia Gravis Model Mice

Effects of Natural Moxibustion at "Feishu （BL 13）" on Th17/Treg Immune Balance and Inflammatory Response in Healthy Rats

Effects of Yinqi Sanhuang Jiedu Decoction （茵芪三黄解毒汤） on Liver Hardness and Epithelial Mesenchymal Transition in Hepatic Fibrosis Model Mice

Effect of Shengyang Yiwei Decoction （升阳益胃汤） on Histopathology， Serum Inflammatory Factors and Peripheral Blood Th17/Treg Balance in Chronic Obstructive Pulmonary Disease Model Rats with Lung-spleen Qi Deficiency Syndrome

Related Author

LYU Wenliang

SHEN Yaocun

WANG Yi

OUYANG Jiqi

LIU Ruge

ZHANG Jie

WANG Jiahui

LIU Hanbin

Related Institution

Graduate School，Beijing University of Chinese Medicine

Guang 'anmen Hospital，China Academy of Chinese Medical Sciences

Hennan Institute of Medical and Pharmaceutical Sciences，Zhengzhou University

The First Clinical Medical College of Henan University of Chinese Medicine

The First Affiliated Hospital of Henan University of Chinese Medicine

Address：No.16, Nanxiao street, Dongzhimen, Dongcheng District, Beijing Postal code：100700
Tel：010-64035632 Email：jtcmcn@188.com
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备09064830号-19 京公网安备11010102007558号
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰

Effect of Fugan Huaxian Decoction （扶肝化纤汤） on Th17/Treg Balance and Related Transcription Factors in Hepatic Fibrosis with Healthy Qi Deficiency and Toxin Accumulation Pattern Model Rats

DOI：10.13288/j.11-2166/r.2023.19.013

摘要

Abstract

关键词

Keywords

references