Astragaloside Ⅳ Attenuates Polymicrobial Sepsis-Induced Cardiac Dysfunction in Rats via IKK/NF-κB Pathway<sup>*</sup>

Xin HUANG; Min-zhou ZHANG; Bo LIU; Shi-yu MA; Xin YIN; Li-heng GUO

doi:10.1007/s11655-021-2869-9

Your Location：

Home >

Browse articles >

Astragaloside Ⅳ Attenuates Polymicrobial Sepsis-Induced Cardiac Dysfunction in Rats via IKK/NF-κB Pathway^*

Original Article | Updated：2021-11-05

- Astragaloside Ⅳ Attenuates Polymicrobial Sepsis-Induced Cardiac Dysfunction in Rats via IKK/NF-κB Pathway^*
- Astragaloside Ⅳ Attenuates Polymicrobial Sepsis-Induced Cardiac Dysfunction in Rats via IKK/NF-κB Pathway^*
- Chinese Journal of Integrative Medicine 2021年27卷第11期页码：825-831
- Affiliations：
  
  1.Intensive Care Research Team of Traditional Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, the Second Clinical Collage of Guangzhou University of Chinese Medicine, Guangzhou (510120), China
  2.Department of Critical Care Medicine, Guangdong Provincial Hospital of Chinese Medicine, the Second Clinical Collage of Guangzhou University of Chinese Medicine, Guangzhou (510120), China
  3.Department of Radiology, Guangdong Provincial Hospital of Chinese Medicine, the Second Clinical Collage of Guangzhou University of Chinese Medicine, Guangzhou (510120), China
- Author bio：
  
  GUO Li-heng, E-mail: guolh782@163.com
- Funds：
  
  Science and Technology Department of Guangdong Province(2014A020212277);Specific Science and Technology Research Fund of Guangdong Province(YN2015QN07)
- DOI：10.1007/s11655-021-2869-9
  中图分类号：
- 纸质出版日期：2021-11-01，
  
  网络出版日期：2021-08-25，
  
  录用日期：2020-09-20
Scan for full text
Xin HUANG, Min-zhou ZHANG, Bo LIU, 等. Astragaloside Ⅳ Attenuates Polymicrobial Sepsis-Induced Cardiac Dysfunction in Rats via IKK/NF-κB Pathway^*[J]. Chinese Journal of Integrative Medicine, 2021,27(11):825-831.

Xin HUANG, Min-zhou ZHANG, Bo LIU, et al. Astragaloside Ⅳ Attenuates Polymicrobial Sepsis-Induced Cardiac Dysfunction in Rats via IKK/NF-κB Pathway^*[J]. Chinese Journal of Integrative Medicine, 2021,27(11):825-831.
Xin HUANG, Min-zhou ZHANG, Bo LIU, 等. Astragaloside Ⅳ Attenuates Polymicrobial Sepsis-Induced Cardiac Dysfunction in Rats via IKK/NF-κB Pathway^*[J]. Chinese Journal of Integrative Medicine, 2021,27(11):825-831. DOI： 10.1007/s11655-021-2869-9.

Xin HUANG, Min-zhou ZHANG, Bo LIU, et al. Astragaloside Ⅳ Attenuates Polymicrobial Sepsis-Induced Cardiac Dysfunction in Rats via IKK/NF-κB Pathway^*[J]. Chinese Journal of Integrative Medicine, 2021,27(11):825-831. DOI： 10.1007/s11655-021-2869-9.

摘要

目的:

在盲肠穿孔结扎法制备脓毒症大鼠模型的基础上

评价黄芪甲苷对脓毒症大鼠心功能障碍的保护作用.

方法:

采用盲肠穿孔结扎法制备脓毒症心功能障碍模型

50 只大鼠按照随机表格分 5 组

假手术( Sham) 组、模型组 ( CLP-18 h/72h) 组和黄芪甲苷干预 ( AST18h/72 h) 组. Sham 组除不对盲肠进行结扎穿孔外

余操作同CLP组; CLP 组和 AST 组分别在造模后给予生理盐水和黄芪甲苷灌胃(40 mg/kg)

每日一次. 酶联免疫吸附法(ELISA)检测不同时间点脓毒症大鼠血清中炎症介质和氧化应激标志物的水平

如白介素6 (IL-6)、高迁移率族蛋白-B1(HMGB1)和超氧化物歧化酶(SOD)、丙二醛(MDA). 通过超声、苏木素-伊红染色心脏组织、血清乳酸脱氢酶(LDH)和肌酸激酶同工酶(CK-MB)表达水平检测各组大鼠心功能及心肌损伤程度. 末端脱氧核苷转移酶介导的缺口末端标记(TUNEL)法分析各组大鼠心肌细胞凋亡水平. 免疫印迹法检测各组大鼠心肌组织B淋巴细胞瘤-2基因 (Bcl-2)、Bcl-2相关X (Bax)、IκB激酶α (IKKα)、NF-κB p65的蛋白表达水平. 并记录各组大鼠的生存时间.

结果:

AST干预后

脓毒症大鼠存活率显著提高到33.3%; (

0.05)

超声结果显示AST能够提高脓毒症大鼠心脏的射血分数、左室缩短分数和左室舒张末期内径(

0.01或

0.05); AST组大鼠心脏组织损伤明显好转

心肌细胞凋亡减少

Bcl-2/Bax比值升高

血清中IL-6、HMGB-1、MDA、LDH、CK-MB水平均有下降(

0.01 或

0.05)

SOD水平上升(

0.01). 而且

AST能够抑制由脓毒症诱导的IKK-α和NF-κB p65磷酸化水平.

结论:

黄芪甲苷能够改善脓毒症大鼠心功能障碍

其作用机制与IKK/NF-κB通路相关.

Abstract

Objective:

To evaluate the protective effects of Astragaloside Ⅳ (AST) in a rat model of myocardial injury induced by cecal ligation and puncture (CLP).

Methods:

The model of sepsis-induced cardiac dysfunction was induced by CLP. Using a random number table

50 specific pathogen free grade of Sprague Dawley rats were randomized into 5 groups: the sham group (sham)

the model group (CLP

18 h/72 h) and AST group (18 h/72 h). Except the sham group

the rats in other groups received CLP surgery to induce sepsis. CLP groups received intragastric administration with normal saline after CLP. AST groups received intragastric administration with AST solution (40 mg/kg) once a day. The levels of inflammatory mediators and oxidative stress markers in the serum of the septic rats were determined via enzyme-linked immunosorbent assay (ELISA) at different time point

such as interleukin 6 (IL-6)

IL-10

high mobility group box-1 protein B1 (HMGB-1)

superoxide dismutase (SOD)

and malondialdehyde (MDA). Cardiac function was determined by echocardiography. Moreover

changes in myocardial pathology were evaluated using hematoxylin and eosin staining. The levels of lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) were analysed to determine the status of CLP-induced myocardium. In addition

the apotosis of myocardial cells was analysed by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL). The protein levels of B-cell lymphoma-2 (Bcl-2)

Bcl-2-associated X (Bax)

IκB kinase α (IKKα)

nuclear factor kappa B p65 (NF-κB p65) were detected by Western blot analysis. Moreover

survival rate was investigated.

Results:

AST improved the survival rate of CLP-induced rats by up to 33.3% (

0.05). The cardioprotective effect of AST was observed by increased ejection fraction

fractional shortening and left ventricular internal diameter in diastole respectively (

0.01 or

0.05). Subsequently

AST attenuated CLP-induced myocardial apoptosis and the ratio of Bcl-2/Bax in the myocardium

as well as the histological alterations of myocardium (

0.01 or

0.05); the generation of inflammatory cytokines (IL-6

IL-10

HMGB-1) and oxidative stress markers (SOD

MDA) in the serum was significantly alleviated (

0.01 or

0.05). On the other hand

AST markedly suppressed CLP-induced accumulation of IKK-α and NF-κB p65 subunit phosphorylation (

0.01 or

0.05).

Conclusions:

AST plays a significant protective role in sepsis-induced cardiac dysfunction and survival outcome. The possible mechanism of cardioprotection is dependent on the activation of the IKK/NF-κB pathway in cardiomyocytes.

关键词

Keywords

Astragaloside Ⅳcecal ligation and puncturemyocardial dysfunction

references

Kim JS, Kim M, Kim YJ, Ryoo SM, Sohn CH, Ahn S, et al.Troponin testing for assessing sepsis-induced myocardial dysfunction in patients with septic shock. J Clin Med 2019;8:239.

Song P, Shen DF, Meng YY, Kong CY, Ma ZG. Geniposide protects against sepsis-induced myocardial dysfunction through AMPKα-dependent pathway. Free Radic Biol Med 2020;152:186-196.

Walley KR. Sepsis-induced myocardial dysfunction. Curr Opin Crit Care 2018;24:292-299.

Zhang CH, Yang X, Wei JR, Chen NM, Xu JP, Bi YQ, et al. Ethnopharmacology, phytochemistry, pharmacology, toxicology and clinical applications of Radix Astragali. Chin J Integr Med 2019:1-12.

Ren Y, Dai YF, Yin X, Wu SX, Guo LH, Zhang MZ. Clinical efficacy of benefiting qi for strengthening resistance on sepsis and inflammatory reaction: a clinical observation of 30 cases.Guid J Tradit Chin Med Pharm (Chin) 2013;19:26-28, 31.

Liao PD, Chen KJ, Ge JB, Zhang MZ. Clinical practice guideline of integrative Chinese and Western medicine for acute myocardial infarction. Chin J Integr Med 2019;26:539-551.

Chen L, Chen XY, Wang QL, Yang SJ, Zhou H, Ding LS, et al. Astragaloside Ⅳ derivative (LS-102) alleviated myocardial ischemia reperfusion injury by inhibiting Drp1 phosphorylation-mediated mitochondrial fission. Front Pharmacol 2020;11:1083.

Kim SH, Ezhilarasan R, Phillips E, Daniel GP, Sparks A, Taylor D, et al. Serine/threonine kinase MLK4 determines mesenchymal identity in glioma stem cells in an NF-kappaB-dependent manner. Cancer Cell 2016;29:201-213.

Liu F, Xia Y, Parker AS, Verma IM. IKK biology. Immunol Rev 2012;246:239-253.

Yamamoto M, Taguchi Y, Ito-Kureha T, Semba K, Yamaguchi N, Inoue JI. NF-kappa B non-cell-autonomously regulates cancer stem cell populations in the basal-like breast cancer subtype. Nat Commun 2013;4:2299.

Rittirsch D, Hoesel LM, Ward PA. The disconnect between animal models of sepsis and human sepsis. J Leukoc Biol 2007;81:137-143.

Chang CP, Liu YF, Lin HJ, Hsu CC, Cheng BC, Liu WP, et al. Beneficial effect of astragaloside on Alzheimer's disease condition using cultured primary cortical cells under β-amyloid exposure. Mol Neurobiol 2016;53:7329-7340.

Lu M, Tang F, Zhang J, Luan A, Mei M, Xu C, et al.Astragaloside Ⅳ attenuates injury caused by myocardial ischemia/reperfusion in rats via regulation of toll-like receptor 4/nuclear factor-kappa B signaling pathway.Phytother Res 2015;29:599-606.

Huang X, Guo LH, Wang L, Huang JA, Zhang MZ.Protection of astragaloside on the peripheral blood endothelial progenitor cells. Pharmacol Clin Chin Mater Med (Chin) 2012;28:26-29.

Zhao P, Wang Y, Zeng S, Lu J, Jiang TM, Li YM. Protective effect of astragaloside Ⅳ on lipopolysaccharide-induced cardiac dysfunction via down-regulation of inflammatory signaling in mice. Immunopharmacol Immunotoxicol 2015;37:428-433.

Zanotti-Cavazzoni SL, Hollenberg SM. Cardiac dysfunction in severe sepsis and septic shock. Curr Opin Crit Care 2009;15:392-397.

Ju Y, Yu K, Wang G. Budesonide ameliorates lung injury induced by large volume ventilation. BMC Pulm Med 2016;16:90.

Lee W, Ku SK, Lee YM, Bae JS. Anti-septic effects of glyceollins in HMGB1-induced inflammatory responses in vitro and in vivo. Food Chem Toxicol 2014;63:1-8.

Sun DW, Gao Q, Qi X. Danshensu ameliorates cardiac ischemia reperfusion injury through activating Sirt1/FoxO1/Rab7 signal pathway. Chin J Integr Med 2020;26:283-291.

Yang J, Zong X, Wu G, Lin S, Feng Y, Hu J. Taurine increases testicular function in aged rats by inhibiting oxidative stress and apoptosis. Amino Acids 2015;47:1549-1558.

Suffredini AF, Fromm RE, Parker MM, Brenner M, Kovacs JA, Wesley RA, et al. The cardiovascular response of normal humans to the administration of endotoxin. N Engl J Med 1989;321:280-287.

Xu Y, Zhang S, Rong J, Lin Y, Zhang Z. Sirt3 is a novel target to treat sepsis induced myocardial dysfunction by acetylated modulation of critical enzymes within cardiac tricarboxylic acid cycle. Pharmacol Res 2020;159:104887.

Sanfilippo F, Corredor C, Fletcher N, Landesberg G, Benedetto U, Foex P, et al. Diastolic dysfunction and mortality in septic patients: a systematic review and meta-analysis. Intensive Care Med 2015;41:1004-1013.

Gamkrelidze M, Intskirveli N, Vardosanidze K, Goliadze L, Chikhladze KH, Ratiani L. Myocardial dysfunction during septic shock. Georgian Med News 2014;40-46.

Zhou X, Zhang L, Lie L, Zhang Z, Zhu B, Yang J, et al. MxA suppresses TAK1-IKKα/β-NF-κB mediated inflammatory cytokine production to facilitate mycobacterium tuberculosis infection. J Infect 2020;81:231-241.

Lawrence T, Bebien M, Liu GY, Nizet V, Karin M. IKK alpha limits macrophage NF-kappa B activation and contributes to the resolution of inflammation. Nature 2005;434:1138-1143.

Shembade N, Harhaj EW. Regulation of NF-kappa B signaling by the A20 deubiquitinase. Cell Mol Immunol 2012;9:123-130.

Zhang Y, Yang X, Ge X, Zhang F. Puerarin attenuates neurological deficits via Bcl-2/Bax/cleaved caspase-3 and Sirt3/SOD2 apoptotic pathways in subarachnoid hemorrhage mice. Biomed Pharmacother 2019;109:726-733.

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

暂无数据