生脉散对DCM大鼠的干预作用及对TLR-4/NF-B炎症信号通路的影响

邢清敏; 陆曙; 周永华; 李岚; 周春刚; 沈丽娟

doi:10.13422/j.cnki.syfjx.2018020128

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生脉散对DCM大鼠的干预作用及对TLR-4/NF-B炎症信号通路的影响

药理 | 更新时间：2024-01-04

- 生脉散对DCM大鼠的干预作用及对TLR-4/NF-B炎症信号通路的影响
- Effect of Shengmaisan on DCM Rats and TLR-4/NF-B Inflammatory Signal Pathway
- 中国实验方剂学杂志 2018年24卷第2期页码：128-134
- 作者机构：
- 作者简介：
- 基金信息：
  
  无锡市医院管理中心科研项目（YGZXM14047）
- DOI：10.13422/j.cnki.syfjx.2018020128
  中图分类号： R285.5
- 纸质出版日期：2018
- 稿件说明：
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邢清敏, 陆曙, 周永华, 等. 生脉散对DCM大鼠的干预作用及对TLR-4/NF-B炎症信号通路的影响[J]. 中国实验方剂学杂志, 2018,24(2):128-134.

XING Qing-min, LU Shu, ZHOU Yong-hua, et al. Effect of Shengmaisan on DCM Rats and TLR-4/NF-B Inflammatory Signal Pathway[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(2): 128-134.
邢清敏, 陆曙, 周永华, 等. 生脉散对DCM大鼠的干预作用及对TLR-4/NF-B炎症信号通路的影响[J]. 中国实验方剂学杂志, 2018,24(2):128-134. DOI： 10.13422/j.cnki.syfjx.2018020128.

XING Qing-min, LU Shu, ZHOU Yong-hua, et al. Effect of Shengmaisan on DCM Rats and TLR-4/NF-B Inflammatory Signal Pathway[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(2): 128-134. DOI： 10.13422/j.cnki.syfjx.2018020128.

摘要

目的：研究生脉散对扩张型心肌病（dilated cardiomyopathy，DCM）大鼠的干预作用，探讨生脉散对Toll样受体-4（Toll like receptor-4，TLR-4）/核转录因子-κB（nuclear factor kappa B，NF-κB）信号通路及炎症因子的影响。方法：用腹腔注射阿霉素法建立DCM大鼠模型，将大鼠随机分为空白组、阿霉素组、生脉散组、培哚普利组，分别采用生脉散和培哚普利对DCM大鼠进行干预。治疗后对大鼠行心脏超声检查；用酶联免疫吸附测定法（ELISA）检测血清B型钠尿肽（BNP），肿瘤坏死因子-α（TNF-α）及白细胞介素-6（IL-6）水平；用实时荧光定量PCR法（Real-time PCR）法检测心肌组织TLR-4，NF-κB mRNA表达水平；用蛋白质印迹法（Western blot）检测心肌组织TLR-4，NF-κB蛋白表达水平；取大鼠左室心肌组织用苏木素-伊红（HE）染色和透射电子显微镜的方法观察大鼠心肌组织形态。结果：与空白组比较，阿霉素组左室舒张末期内径（LVIDd），左室收缩末期内径（LVIDs）增大（P<0.01），左心室射血分数（LVEF），短轴缩短率（FS）下降（P<0.01）；血清BNP，TNF-α，IL-6水平升高（P<0.01）；心肌组织TLR-4，NF-κB mRNA及蛋白表达水平升高（P<0.01）；心肌组织病理损伤增加。与阿霉素组比较，生脉散组LVIDs，LVIDd减小（P<0.01），LVEF，FS增加（P<0.01）；血清BNP，TNF-α，IL-6水平下降（P<0.01）；心肌组织TLR-4，NF-κB mRNA及蛋白表达水平下降（P<0.01），心肌组织病理损伤有所改善。结论：生脉散可有效改善DCM大鼠心功能，抑制心肌损害。生脉散治疗DCM大鼠的作用机制，可能与调节TLR-4和NF-κB mRNA及蛋白水平从而抑制TLR-4/NF-κB信号通路下游炎症因子有关。

Abstract

Objective:To evaluate the effect of Shengmaisan on rats with dilated cardiomyopathy (DCM)

Toll-like receptor-4(TLR-4)/nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB) signaling pathway as well as inflammatory factors. Method:The establishment of dilated cardiomyopathy rats model was induced through intraperitoneal injection with doxorubicin (1 mg·kg-1

twice a week) for 6 weeks

and then observed for 2 weeks

which lasted for eight weeks in total. The rats were randomly divided into four groups:blank group

doxorubicin group

Shengmaisan group and perindopril group. The drug groups were given Shengmaisan and perindopril

while blank group and model group were given equal volume of normal saline. left ventricular internal diameter at end-diastole(LVIDd)

left ventricular internal dimenter at end-systole(LVIDs)

left ventricular ejection fraction(LVEF) and fractional shortening(FS) were measured by echocardiography. Then the levels of serum brain natriuretic peptide(BNP) and inflammatory factors

including tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) were tested by enzyme-linked immunosorbent assay (ELISA). TLR-4

NF-κB mRNAs and proteins expressions in rat cardiac muscle were respectively determined. Histopathological characteristics of left ventricular cardiac muscle were observed by hematoxylin-eosin(HE) staining and transmission electron microscopy. Result:Compared with blank group

LVIDd and LVISd in the doxorubicin group were increased significantly(P<0.01); LVEF and FS were decreased significantly. Rats serum BNP

TNF-α and IL-6 levels increased significantly(P<0.01); TLR-4

NF-κB mRNA and protein expressions were increased significantly(P<0.01). And the pathological damage of myocardium was increased. Compared with doxorubicin group

LVIDd and LVISd in the Shengmaisan group were decreased significantly(P<0.01); LVEF and FS were increased significantly

Rat serum BNP

TNF-α and IL-6 levels decreased significantly(P<0.01); TLR-4

NF-κB mRNA and protein expressions were decreased significantly(P<0.01). And pathological damage in myocardial tissues was alliviated. Conclusion:Shengmaisan can effectively improve cardiac function and restrain myocardial damage of DCM rats. The mechanisms of action of Shengmaisan can regulate partly TLR-4 and NF-κB mRNA and protein expressions of rats with dilated cardiomyopathy

and restrain downstream inflammatory factors in TLR-4/NF-κB signaling pathways.

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