化瘀祛痰方对ApoE<sup>－/－</sup>小鼠主动脉MAPK信号通路相关蛋白表达的影响

冷雪; 李阳; 宋囡; 王莹

doi:10.13422/j.cnki.syfjx.20190291

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化瘀祛痰方对ApoE^－/－小鼠主动脉MAPK信号通路相关蛋白表达的影响

药理 | 更新时间：2021-02-09

- 化瘀祛痰方对ApoE^－/－小鼠主动脉MAPK信号通路相关蛋白表达的影响
- Effect of Huayu Qutan Recipe in Regulating Aortic MAPK Pathway-related Gene Expression in Atherosclerosis Mice
- 中国实验方剂学杂志 2019年25卷第4期页码：116-121
- 作者机构：
  
  辽宁中医药大学　中医脏象理论及应用教育部重点实验室，沈阳　 110847
- 作者简介：
  
  *冷雪，硕士，实验师，从事中药防治心血管疾病分子生物学机制研究，Tel：024-31207046，E-mail：290404025@qq.com
- 基金信息：
  
  辽宁省自然科学基金指导计划项目(20170540592);沈阳市科技计划项目(17-139-8-00);辽宁省教育厅科学研究一般项目(L2015332)
- DOI：10.13422/j.cnki.syfjx.20190291
  中图分类号： R2-0;R22;R285.5
- 收稿日期：2018-07-01，
  
  纸质出版日期：2019-02-20
- 稿件说明：
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冷雪, 李阳, 宋囡, 等. 化瘀祛痰方对ApoE^－/－小鼠主动脉MAPK信号通路相关蛋白表达的影响[J]. 中国实验方剂学杂志, 2019,25(4):116-121.

Xue LENG, Yang LI, Nan SONG, et al. Effect of Huayu Qutan Recipe in Regulating Aortic MAPK Pathway-related Gene Expression in Atherosclerosis Mice[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(4): 116-121.
冷雪, 李阳, 宋囡, 等. 化瘀祛痰方对ApoE^－/－小鼠主动脉MAPK信号通路相关蛋白表达的影响[J]. 中国实验方剂学杂志, 2019,25(4):116-121. DOI： 10.13422/j.cnki.syfjx.20190291.

Xue LENG, Yang LI, Nan SONG, et al. Effect of Huayu Qutan Recipe in Regulating Aortic MAPK Pathway-related Gene Expression in Atherosclerosis Mice[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(4): 116-121. DOI： 10.13422/j.cnki.syfjx.20190291.

摘要

目的：

探讨载脂蛋白敲除(Apoe

－/－

)小鼠主动脉丝裂原活化蛋白激酶(MAPK)信号通路相关mRNA的表达变化及化瘀祛痰方药对其的干预作用，探讨化瘀祛痰方药抗AS作用及可能的机制。

方法：

50只ApoE

－/－

小鼠随机分为模型组，丹参酮ⅡA组(30 mg·kg

－1

·d

－1

)，化瘀祛痰高剂量组(20 g·kg

－1

·d

－1

)，化瘀祛痰中剂量组(10 g·kg

－1

·d

－1

)，化瘀祛痰低剂量组(5 g·kg

－1

·d

－1

)，10只C57BL/6/J小鼠作为正常组。全自动生化仪检测血清甘油三酯(triglyceride，TG)，胆固醇(cholesterol，TC)，高密度脂蛋白胆固醇(high-density lipoprotein cholesterol，HDL-C)，低密度脂蛋白胆固醇(low-density lipoprotein cholesterol，LDL-C)的含量；苏木素-伊红(HE)检测各组小鼠主动脉斑块情况；油红O检测各组小鼠肝脏脂质沉积情况；酶联免疫吸附测定(ELISA)测定各组小鼠血清中血管细胞黏附分子-1(vascular cell adhesion protein 1，VCAM-1)，细胞间黏附分子-1(ICAM-1)，白细胞介素-6(interleukin-6，IL-6)，肿瘤坏死因子-

(tumor necrosis factor-

，TNF-

)含量；蛋白免疫印迹法(Western blot)检测各组小鼠主动脉c-Jun氨基末端激酶(c-Jun

-terminal kinase，JNK)，磷酸化c-Jun氨基末端激酶(phosphorylated c-Jun

-terminal kinase，p-JNK)，p38 MAPK，p-p38 MAPK，细胞外调节激酶(extracellular regulated protein kinases，ERK)，磷酸化细胞外调节激酶(extracellular regulated protein kinases，p-ERK)蛋白的表达变化。

结果：

与正常组比较，模型组小鼠血清TC，TG，LDL-C水平明显升高，HDL-C水平明显降低；主动脉管腔见较大粥样斑块，肝细胞中见大量脂质沉积；血清内相关炎性因子TNF-

，IL-6，VCAM-1，ICAM-1含量增加；血管内相关MAPK信号通路p-p38，p-JNK蛋白表达明显增加(

0.05)。与模型组比较，丹参酮ⅡA组与化瘀祛痰各组小鼠TC，TG，LDL-C明显下降，HDL-C明显升高，主动脉管腔中粥样斑块面积和肝脏脂质沉积量明显减少，血清内相关炎性因子TNF-

，IL-6，VCAM-1，ICAM-1含量降低(

0.05)；血管内相关MAPK信号通路p-p38，p-JNK蛋白表达明显降低(

0.05)，p-ERK表达趋势不明显。

结论：

化瘀祛痰方药可抑制ApoE

－/－

小鼠主动脉斑块形成，其机制可能与调控血管MAPK信号通路基因表达有关。

Abstract

Objective:

To investigate the expression changes of mitogen activated protein kinase(MAPK) signaling pathway-related genes in ApoE

-/-

mice and the intervention effect of Huayu Qutan recipe on them

in order to explore the anti-atherosclerotic(AS) effect and possible mechanism of Huayu Qutan recipe.

Method:

Fifty ApoE

-/-

mice were randomly divided into model group

tanshinone IIA group (30 mg·kg

-1

·d

-1

)

and high-dose phlegm group (20 g·kg

-1

·d

-1

)

the middle-dose group (10 g·kg

-1

·d

-1

)

and the low-dose group (5 g·kg

-1

·d

-1

)

and 10 C57BL/6/J mice were included in the blank controls group. Automated biochemical analyzer was used to detect serum triglyceride(TG)

cholesterol(TC)

high-density lipoprotein cholesterol(HDL-C)

low-density lipoprotein cholesterol(LDL-C) content; hematoxylin-eosin(HE) was used to detect aortic plaque in each group; oil red O was used to detect liver lipid deposition in each group; enzyme-linked immuno sorbent assay(ELISA) was used to determine vascular cell adhesion protein-1(VCAM-1)

intercellular adhesion molecule-1(ICAM-1)

interleukin-6(IL-6)

tumor necrosis factor-

(TNF-

) in serum of each group; Western blot was performed to detect c-Jun N-terminal kinase (JNK)

phosphorylated c-Jun

-terminal kinase(p-JNK)

c-Jun N-terminal kinase(JNK)

p38 MAPK

p-p38 MAPK

extracellular regulated protein kinases (ERK)

and expression of p-ERK.

Result:

Compared with the blank control group

serum TC

LDL-C levels in the model group were significantly increased

while HDL-C levels were significantly decreased; aortic plaques were observed in the aortic lumen

and lots of lipid deposition were observed in the liver cells. Serum inflammatory factors TNF-

IL-6

VCAM-1

ICAM-1 increased(

0.05); and intravascular associated MAPK signaling pathway p-p38 MAPK

p-JNK gene expressions increased significantly(

0.05). Compared with the model group

LDL-C in the tanshinone IIA group and the phlegm group were significantly decreased

HDL-C was significantly increased

and atherosclerotic plaque area and liver lipid were remarkably reduced in the aortic lumen. The deposition amount was significantly reduced

and the levels of inflammatory factors such as TNF-

IL-6

VCAM-1 and ICAM-1 were decreased. The expressions of p-p38 MAPK and p-JNK genes in intravascular associated MAPK signaling pathway were significantly decreased. p-ERK expression trend was not obvious(

0.05).

Conclusion:

Huayu Recipe can inhibit the formation of aortic plaque in ApoE

-/-

mice

and its mechanism may be related to the regulation of vascular MAPK signaling pathway gene expression.

关键词

Keywords

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化瘀祛痰方对ApoE－/－小鼠主动脉MAPK信号通路相关蛋白表达的影响

Effect of Huayu Qutan Recipe in Regulating Aortic MAPK Pathway-related Gene Expression in Atherosclerosis Mice

DOI：10.13422/j.cnki.syfjx.20190291

摘要

Abstract

关键词

Keywords

references

化瘀祛痰方对ApoE^－/－小鼠主动脉MAPK信号通路相关蛋白表达的影响