Effect of Shugan Wendan Decoction on LXRα, NF-кB and Endothelial Function in Atherosclerosis Rabbits

Shuai ZHAO; Lie-yuan ZHANG; Wen-wei FENG; Wei-zhang ZHANG; Yong-ning GUO; Zi-cong ZHAO; Bo-jun CHEN

doi:10.13422/j.cnki.syfjx.20191639

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Effect of Shugan Wendan Decoction on LXRα, NF-кB and Endothelial Function in Atherosclerosis Rabbits

Pharmacology | 更新时间：2021-02-09

- Effect of Shugan Wendan Decoction on LXRα, NF-кB and Endothelial Function in Atherosclerosis Rabbits
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 15, Pages: 108-115(2019)
- 作者机构：
  
  广州中医药大学　第二附属医院，广州　 510006
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20191639
  CLC： R2-0; R289; R285.5; R318.11
- Received：23 February 2019，
  
  Published Online：08 May 2019，
  
  Published：05 August 2019
- 稿件说明：
移动端阅览
Shuai ZHAO, Lie-yuan ZHANG, Wen-wei FENG, et al. Effect of Shugan Wendan Decoction on LXRα, NF-кB and Endothelial Function in Atherosclerosis Rabbits[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(15): 108-115.
DOI：

Shuai ZHAO, Lie-yuan ZHANG, Wen-wei FENG, et al. Effect of Shugan Wendan Decoction on LXRα, NF-кB and Endothelial Function in Atherosclerosis Rabbits[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(15): 108-115. DOI： 10.13422/j.cnki.syfjx.20191639.

摘要

目的：

基于肝X受体

/核转录因子-

B(LXR

/NF-

B)通路探讨疏肝温胆汤对家兔动脉粥样硬化的作用及机制。

方法：

采用小牛血清白蛋白免疫损伤、高脂饲养和束缚情志应激的方法建立肝郁型的新西兰兔动脉粥样硬化模型。随机分为6组，分别为正常组，模型组，阿托伐他汀组，疏肝温胆汤低、中、高剂量组(2.18，6.54，19.62 g·kg

－1

·d

－1

)。造模成功后，分别给予阿托伐他汀、疏肝温胆汤低、中、高剂量灌胃，正常组和模型组均予同浓度生理盐水灌胃。连续灌胃6周。给药结束后，采用苏木素-伊红(HE)染色法检测各组主动脉的病理变化；分别采用酶法、硝酸还原酶法和酶联免疫吸附测定(ELISA)检测各组血清中总胆固醇(TC)，甘油三酯(TG)，低密度脂蛋白胆固醇(LDL-C)，高密度脂蛋白胆固醇(HDL-C)，一氧化氮(NO)和内皮素-1(ET-1)的水平；采用实时荧光定量PCR(Real-time PCR)检测主动脉组织中C反应蛋白(CRP)，白细胞介素-1

(IL-1

)，白细胞介素-6(IL-6)和基质金属蛋白酶-9(MMP-9)mRNA的表达；采用蛋白免疫印迹法(Western blot)检测主动脉组织的LXR

/NF-

B信号通路蛋白的表达。

结果：

与正常组比较，模型组血管腔明显狭窄，粥样斑块形成明显，可见大量的细胞内泡沫样改变，而阿托伐他汀组和疏肝温胆汤高、中、低剂量组的血管狭窄、粥样斑块及泡沫样改变的程度均较模型组低。与正常组比较，模型组的TG，TC和LDL-C升高(

0.05)，HDL降低(

0.05)，血清中NO明显降低(

0.05)，ET-1明显升高(

0.05)，hs-CRP，IL-1

，IL-6和MMP-9的表达均明显升高(

0.05)，LXR

的蛋白表达明显降低(

0.05)，NF-

B的蛋白表达明显升高(

0.05)；与模型组比较，阿托伐他汀及疏肝温胆汤低、中、高剂量组的TG，TC和LDL-C含量明显降低(

0.05)，阿托伐他汀组和疏肝温胆汤高剂量组血清中NO明显升高(

0.05)，ET-1明显降低(

0.05)，阿托伐他汀组及疏肝温胆汤低、中、高剂量组中CRP，IL-1

，IL-6和MMP-9的表达量均降低(

0.05)，阿托伐他汀组、疏肝温胆汤各剂量组中LXR

的蛋白表达量均升高(

0.05)，NF-

B的蛋白表达均明显降低(

0.05)。

结论：

疏肝温胆汤通过调控LXR

/NF-

B信号通路改善血管内皮细胞功能和动脉粥样斑块的稳定性，从而发挥抗动脉粥样硬化效应。

Abstract

Objective:

To investigate the mechanism of Shugan Wendan decoction in treating atherosclerosis based on liver X receptor

(LXR

)/nuclear factor-

B(NF-

B) signal.

Method:

A New Zealand rabbit model of atherosclerosis with liver-Qi stagnation was established by using calf serum albumin immune injury

high fat feeding and bondage emotional stress method. Theses rabbits are randomly divided into 6 groups

control group

model group

atorvastatin group

Shugan Wendan decoction low

medium and high dose group(2.18

6.54

19.62 g·kg

-1

·d

-1

). After successful modeling

the rabbits were treated by injecting drugs with Atorvastatin and low

middle and high dose Shugan Wendan decoction to gastric.The control group and the model group were given intragastric administration of saline in the same volume. The period of gavage is 6 weeks. The pathological changes of the rabbits were detected by hematoxylin-eosin(HE) staining.Serum levels of totalcholesterol(TC)

triglyceride(TG)

low density extremityprotein(LDL-C)

high density extremity protein(HDL-C)

nitric oxide(NO)

and endothelin-1(ET-1) of the rabbits were detected by enzyme method

nitrate reductase method

and enzyme-linked immunosorbent assay(ELISA)

respectively.The gene expression of CRP

IL-1

IL-6 and MMP-9 in the aorta was detected by Real-time fluorescent quantitative polymerase chain reaction(Real-time PCR) method.The protein expression of LXR

/NF-

B signaling pathway wasdetected by Western blot.

Result:

Compared with normal control group

in model group

the lumen of the blood vessels was significantly narrowed

atheromatous plaques were formed

and a large number of intracellular foam-like changes were seen. In atorvastatin group and Shugan Wendan decoction group

the blood vessels in high

middle

and low concentration groups were narrowed. Atherosclerotic plaques and foam-like changes were all lower than the model group.Compared with the normal control group

the TG

and LDL-C levels in the model groupincreased(

0.05)

HDL decreased (

0.05)

NO decreased (

0.05)

ET-1 increased (

0.05)

the expression levels of hs-CRP

IL-1

IL-6 and MMP-9 all increased(

0.05)

the expression of LXR

protein in the model group was decreased(

0.05)

and the protein expression of NF-

B was increased(

0.05). Compared with model group

the levels of TG

TC and LDL-C the atorvastatin group andlow

medium

and highdose Shugan Wendan decoction group decreased

(

0.05)

NO in the atorvastatin group and the highdose Shugan Wendan decoction group increased and ET-1 decreased(

0.05). In group comparison

the expression levels of CRP

IL-1

IL-6 and MMP-9 in the atorvastatin group

the low

middle and high dose Shugan Wendan decoction groups all decreased(

0.05). The expression of LXR

protein in the group was increased(

0.05) and the protein expression of NF-

B was decreased(

0.05).

Conclusion:

Shugan Wendan decoction can inhance the function of vascular endothelial cells and the stability of atherosclerotic plaque by regulating LXR

/NF-

B signaling pathway.

关键词

Keywords

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