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Astragaloside Ⅳ Attenuates Polymicrobial Sepsis-Induced Cardiac Dysfunction in Rats via IKK/NF-κB Pathway*
- Chinese Journal of Integrative Medicine Vol. 27, Issue 11, Pages: 825-831(2021)
- 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：
DOI：10.1007/s11655-021-2869-9
CLC：Published：01 November 2021，
Published Online：25 August 2021，
Accepted：20 September 2020
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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 27(11):825-831(2021)
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 27(11):825-831(2021) DOI： 10.1007/s11655-021-2869-9.
摘要
目的:
2
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:
2
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:
2
AST干预后
脓毒症大鼠存活率显著提高到33.3%; (
P
<
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(
P
<
0.01或
P
<
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(
P
<
0.01 或
P
<
0.05)
SOD水平上升(
P
<
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:
2
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:
2
To evaluate the protective effects of Astragaloside Ⅳ (AST) in a rat model of myocardial injury induced by cecal ligation and puncture (CLP).
Methods:
2
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:
2
AST improved the survival rate of CLP-induced rats by up to 33.3% (
P
<
0.05). The cardioprotective effect of AST was observed by increased ejection fraction
fractional shortening and left ventricular internal diameter in diastole respectively (
P
<
0.01 or
P
<
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 (
P
<
0.01 or
P
<
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 (
P
<
0.01 or
P
<
0.05). On the other hand
AST markedly suppressed CLP-induced accumulation of IKK-α and NF-κB p65 subunit phosphorylation (
P
<
0.01 or
P
<
0.05).
Conclusions:
2
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
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