黄芩素通过削弱T淋巴细胞免疫功能障碍和炎症以缓解严重脓毒症

Hai-yan CHEN; Shu ZHANG; Jun LI; Na HUANG; Jin SUN; Bao-hua LI; Jun YANG; Zong-fang LI

doi:10.1007/s11655-022-3510-7

Your Location：

Home >

Browse articles >

黄芩素通过削弱T淋巴细胞免疫功能障碍和炎症以缓解严重脓毒症

Original Article | Updated：2022-07-20

- 黄芩素通过削弱T淋巴细胞免疫功能障碍和炎症以缓解严重脓毒症
- Baicalein Attenuates Severe Polymicrobial Sepsis via Alleviating Immune Dysfunction of T Lymphocytes and Inflammation
- Chinese Journal of Integrative Medicine 2022年28卷第8期页码：711-718
- Affiliations：
  
  1.National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an (710004), China
  2.Core Research Laboratory, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an (710004), China
  3.Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an (710004), China
  4.Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an (710004),China
  5.Department of Pathology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an (710004), China
- Author bio：
  
  Prof. LI Zong-fang, E-mail: lzf2568@gmail.com
- Funds：
  
  Program for Changjiang Scholars and Innovative Research Team in University, China(IRT1171)
- DOI：10.1007/s11655-022-3510-7
  中图分类号：
- 纸质出版日期：2022-08，
  
  网络出版日期：2022-03-30，
  
  录用日期：2021-06-15
Scan for full text
Hai-yan CHEN, Shu ZHANG, Jun LI, 等. 黄芩素通过削弱T淋巴细胞免疫功能障碍和炎症以缓解严重脓毒症[J]. Chinese Journal of Integrative Medicine, 2022,28(8):711-718.

Hai-yan CHEN, Shu ZHANG, Jun LI, et al. Baicalein Attenuates Severe Polymicrobial Sepsis via Alleviating Immune Dysfunction of T Lymphocytes and Inflammation[J]. Chinese Journal of Integrative Medicine, 2022,28(8):711-718.
Hai-yan CHEN, Shu ZHANG, Jun LI, 等. 黄芩素通过削弱T淋巴细胞免疫功能障碍和炎症以缓解严重脓毒症[J]. Chinese Journal of Integrative Medicine, 2022,28(8):711-718. DOI： 10.1007/s11655-022-3510-7.

Hai-yan CHEN, Shu ZHANG, Jun LI, et al. Baicalein Attenuates Severe Polymicrobial Sepsis via Alleviating Immune Dysfunction of T Lymphocytes and Inflammation[J]. Chinese Journal of Integrative Medicine, 2022,28(8):711-718. DOI： 10.1007/s11655-022-3510-7.

摘要

目的:

探讨黄芩素对脓毒症所诱发的免疫功能障碍和器官损伤的作用研究.

方法:

采用盲肠结扎穿刺法(CLP)建立SD大鼠脓毒症模型. 将无特异致病菌的大鼠随机分为假手术组、CLP组和CLP +黄芩素组 (

= 16/组). CLP + Bai组的大鼠在CLP造模后的1小时和10小时分别静脉注射黄芩素(20 mg/kg). 评估各组大鼠的生存率、细菌载量和器官损伤. 然后在6、12、24 h

对每组进行评估并观察黄芩素对脓毒症大鼠的免疫细胞和炎性细胞因子的影响.

结果:

黄芩素治疗能显著提高脓毒症大鼠的存活率

降低细菌载量

通过苏木精和伊红染色观察到可以减轻组织损伤(脾脏、肝脏和肺). 黄芩素处理后脓毒症大鼠的外周血和脾脏中发现

CD3

CD4

T细胞比例及CD4

/CD8

比值显著升高 (均

0.05). 而且

黄芩素能降低造模后24 h的脓毒症大鼠的白细胞和脾脏细胞凋亡率(

0.05). 黄芩素还能显著降低脾脏中肿瘤坏死因子α和白细胞介素-6 (IL-6)的水平

升高IL-10的水平

并能显著提高galectin - 9的表达水平(

0.01).

结论:

黄芩素可能是一种有效的免疫调节剂

可减轻严重腹腔性脓毒症的压倒性炎症反应.

Abstract

Objective:

To investigate the effect of baicalein on polymicrobial sepsis-induced immune dysfunction and organ injury.

Methods:

A sepsis model was induced in Sprague-Dawley rats via caecal ligation and puncture (CLP). Specific pathogen free rats were randomly divided into a sham group

CLP group and CLP + baicalein (Bai) group (

=16 each). Rats in the CLP + Bai group were intravenously injected with baicalein (20 mg/kg) at 1 and 10 h after CLP. Survival rate

bacterial load

and organ damage were assessed. Then each group was evaluated at 6

and 24 h to investigate the effect of baicalein on immune cells and inflammatory cytokines in septic rats.

Results:

Baicalein treatment significantly improved the survival of septic rats

decreased the bacterial burden

and moderated tissue damage (spleen

liver

and lung)

as observed by haematoxylin and eosin staining. Septic rats treated with baicalein had strikingly increased proportions of CD3

CD4

T cells and ratios of CD4

/CD8

T cells in the peripheral blood and spleen (all

0.05). Moreover

baicalein treatment decreased the apoptotic rate of whole white blood cells and spleen cells at 24 h after surgery (

0.05). Baicalein significantly reduced the levels of tumor necrosis factor α and interleukin-6 (IL-6) and increased IL-10

and the expression levels of galectin 9 were also raised in the spleen (

0.01).

Conclusion:

Baicalein may be an effective immunomodulator that attenuates overwhelming inflammatory responses in severe abdominal sepsis.

关键词

黄芩素中药脓毒症脾脏炎症淋巴细胞

Keywords

baicaleinChinese medicinesepsisspleeninflammationlymphocytes

references

Singer M, Deutschman CS, Seymour CW, Shankar-Hari M,Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). J Am Med Assoc 2016;315:801-810.

Sundararajan V, Maclsaac CM, Presneill JJ, Cade JF,Visvanathan K. Epidemiology of sepsis in Victoria,Australia. Crit Care Med 2005;33:71-80.

Vincent JL, Marshall JC, Namendys-Silva SA, Francois B, Martin-Loeches I, Lipman J, et al. Assessment of the worldwide burden of critical illness: the Intensive Care Over Nations (ICON) audit. Lancet Respir Med 2014;2:380-386.

Hotchkiss RS, Tinsley KW, Swanson PE, Schmieg RE Jr, Hui JJ, Chang KC, et al. Sepsis-induced apoptosis causes progressive profound depletion of B and CD4+ T lymphocytes in humans. J Immunol 2001;166:6952-6963.

Huang N, Ji FP, Zhang S, Li ZZ, Li J, Zhou R, et al. Spleen-associated effects on immunity in hepatitis b virus-related cirrhosis with portal hypertension. J Interferon Cytokine Res 2019;39:95-105.

Bolognese AC, Sharma A, Yang WL, Nicastro J, Coppa GF, Wang P. Cold-inducible RNA-binding protein activates splenic T cell during sepsis in a TLR4-dependent manner.Cell Mol Immunol 2018;15:38-47.

Dkhil MA, Al-Quraishy S, Mineim AEA. Ziziphus spina-christi leaf extract pretreatment inhibits liver and spleen injury in a mouse model of sepsis via anti-oxidant and anti-inflammatory effects. Inflammopharmacology 2018;26:779-791.

Gaire BP, Moon SK, Kim H. Scutellaria baicalensis in stroke management: nature's blessing in traditional Eastern medicine. Chin J Integr Med 2014;20:712-720.

Dou J, Wang Z, Ma L, Peng B, Mao K, Li C, et al. Baicalein and baicalin inhibit colon cancer using two distinct fashions of apoptosis and senescence. Oncotarget 2018;9:20089-20102.

Shen YC, Chiou WF, Chou YC, Chen CF. Mechanisms in mediating the anti-inflammatory effects of baicalin and baicalein in human leukocytes. Eur J Pharmacol 2003;465:171-181.

Gao L, Li JQ, Zhou YZ, Huang XD, Qin XM, Du GH. Effects of baicalein on cortical proinflammatory cytokines and the intestinal microbiome in senescence accelerated mouse prone 8. Acs Chem Neurosci 2018;9:1714-1724.

Lee YM, Cheng PY, Chim LS, Kung CW, Ka SM, Chung MT,et al. Baicalein, an active component of Scutellaria baicalensis Georgi, improve scardiac contractile function in endotoxaemic rats via induction of hemeoxygenase-1 and suppression of inflammatory responses. J Ethnopharmacol 2011;135:179-185.

Wu YL, Lian LH, Ying W, Nan JX. Baicalein inhibits nuclear factor-κB and apoptosis via c-FLIP and MAPK in D-GalN/LPS-induced acute liver failure in murine modes. Chem Biol Interact 2010;188:526-534.

Liu AD, Wang WJ, Fang HS, Yang Y, Jiang XJ, Liu SP, et al. Baicalein protects against polymicrobial sepsis-induced liver injury via inhibition of inflammation and apoptosis in mice. Eur J Pharmacol 2015;748:45-53.

Xiang L, Hu YF, Wu JS, Wang L, Huang WG, Xu CS, et al.Semi-mechanism-based pharmacodynamic model for the anti-inflammatory effect of baicalein in LPS-stimulated RAW 264.7 macrophages. Front Pharmacol 2018;9:793.

Pu WL, Luo YY, Bai RY, Guo AW, Zhou K, Zhang YS,et al. Baicalein inhibits acinar-to-ductal metaplasia of pancreatic acinal cell AR42J via improving the inflammatory microenvironment. J Cell Physiol 2018;233:5747-5755.

Cheng PY, Lee YM, Wu YS, Chang TW, Jin JS, Yen MH.Protective effect of baicalein against endotoxic shock in rats in vivo and in vitro. Biochem Pharmacol 2007;73:793-804.

He X, Wei Z, Zhou E, Chen L, Kou J, Wang J, et al. Baicalein attenuates inflammatory responses by suppressing TLR4 mediated NF-κB and MAPK signaling pathways in LPS-induced mastitis in mice. Int Immunopharmacol 2015;28:470-476.

Suda K, Kitagawa Y, Ozawa S, Saikawa Y, Ueda M, Ebina M, et al. Anti-high-mobility group box chromosomal protein 1 antibodies improve survival of rats with sepsis. World J Surg 2006;30:1755-1762.

Yang H, Ochani M, Li JH, Qiang XL, Tanovic M, Harris HE, et al. Reversing established sepsis with antagonists of endogenous high-mobility group box 1. P Natl Acad Sci USA 2004;101:296-301.

Tang LP, Xiao W, Li YF, Li HB, Wang ZZ, Yao XS, et al. Anti-inflammatory effects of Reduning Injection on lipopolysaccharide-induced acute lung injury of rats. Chin J Integr Med 2014;20:591-599.

Das P, Panda SK, Agarwal B, Behera S, Ali SM, Pulse ME, S. et al. Novel chitohexaose analog protects young and aged mice from CLP-induced polymicrobial sepsis. Sci Rep 2019;27;9:2904.

Yin HF, Huang LH, Ouyang T, Chen LY. Baicalein improves liver inflammation in diabetic db/db mice by regulating HMGB1/TLR4/NF-kappa B signaling pathway. Int Immunopharmacol 2018;55:55-62.

Hu XH, Miao PZ, Yu RH, Zheng HC. The immunoprotective activity of baicalin in mouse model of cecal ligation and puncture-induced sepsis. Cell Biochem Biophys 2015;71:543-547.

Zhang Y, Shan L, Hua YP, Wang D, Zeng HW, Liu RH,et al. Baicalein selectively induces apoptosis in activated lymphocytes and ameliorates concanavalin a-induced hepatitis in mice. Plos One 2013;8:e69592.

Ward PA, Bosmann M. A historical perspective on sepsis.Am J Pathol 2012;181:2-7.

Hasan Z, Palani K, Zhang S, Lepsenyi M, Hwaiz R,Rahman M, et al. Rho kinase regulates induction of T-cell immune dysfunction in abdominal sepsis. Infect Immun 2013;81:2499-2506.

Yasuda T, Takeyama Y, Ueda T, Takase K, Nishikawa J,Kuroda Y. Splenic atrophy in experimental severe acute pancreatitis. Pancreas 2002;4:365-372.

Hotchkiss RS, Osmon SB, Chang KC, Wagner TH,Coopersmith CM, Karl IE. Accelerated lymphocyte death in sepsis occurs by both the death receptor and mitochondrial pathways. J Immunol 2005;174:5110-5118.

Zhang Y, Zhou Y, Lou JS, Li JB, Bo LL, Zhu KM, et al. PD-L1 blockade improves survival in experimental sepsis by inhibiting lymphocyte apoptosis and reversing monocyte dysfunction. Crit Care 2010;14:R220.

Sahu BD, Kumar JM, Kuncha M, Borkar RM, Srinivas R, Siatla R. Baicalein alleviates doxorubicin-induced cardiotoxicity via suppression of myocardial oxidativestress and apoptosis in mice. Life Sci 2016;144:8-18.

Weber GF, Swirski FK. Immunopathogenesis of abdominal sepsis. Langenbecks Arch Surg 2014;399:1-9.

Chen LW, Lu Y, Zhao LJ, Hu LL, Qiu QM, Zhang ZL, et al.Curcumin attenuates sepsis-induced acute organ dysfunction by preventing inflammation and enhancing the suppressive function of Tregs. Int Immunopharmacol 2018;61:1-7.

Xu YJ, Li Y, Liu XH, Pan YC, Sun ZH. SPIONs enhances IL-10-producing macrophages to relieve sepsis via Cav1-Notch1/HES1-mediated autophagy. Int J Nanomed 2019;23:6779-6797.

Kadowaki T, Morishita A, Niki T, Hara J, Sato M, Tani J, et al. Galectin-9 prolongs the survival of septic mice by expanding Tim-3-expressing natural killer T cells and PDCA-1+ CD11c+ macrophages. Crit Care 2013;17:R284.

More>

浏览量

Downloads

CSCD

文章被引用时，请邮件提醒。

Submit

工具集

关联资源

Research Advance of Chinese Medicine in Treating Atherosclerosis: Focus on Lipoprotein-Associated Phospholipase A2

Effectiveness of Acupoint Application in Patients with Pharyngeal Pain: Evidence from CHUNBO,A Prospective Real-World Study

Danhong Injection Up-Regulates miR-125b in Endothelial Exosomes and Attenuates Apoptosis in Post-Infarction Myocardium

Network Pharmacology and Experimental Validation to Explore Mechanism of Tetrahydropalmatine on Acute Myocardial Ischemia

Guanxin Ⅴ Relieves Ventricular Remodeling by Inhibiting Inflammation: Implication from Virtual Screening, Systematic Pharmacology, Molecular Docking, and Experimental Validation