凉血散瘀法通过抑制巨噬细胞凋亡抗动脉粥样硬化的作用

刘学谦; 王静; 曹守沛; 宋耀鸿

doi:10.13422/j.cnki.syfjx.20190336

您当前的位置：

首页 >

文章列表页 >

凉血散瘀法通过抑制巨噬细胞凋亡抗动脉粥样硬化的作用

药理 | 更新时间：2021-02-09

- 凉血散瘀法通过抑制巨噬细胞凋亡抗动脉粥样硬化的作用
- Effect of Cooling Blood Method in Inhibiting Macrophage Apoptosis Against Atherosclerosis
- 中国实验方剂学杂志 2019年25卷第3期页码：59-65
- 作者机构：
  
  1.南京中医药大学，南京　 210023
  2.南京中医药大学　附属南京中医院，南京　 210001
  3.南京市红十字医院，南京　 210001
- 作者简介：
  
  刘学谦，在读硕士，从事中西医心血管方面研究，E-mail: liuxueqian1753@163.com
  *曹守沛，博士，副主任医师，从事中西医心血管病临床研究，Tel: 025-52276242，E-mail: caosp336@126.com;
  *宋耀鸿，博士，副主任医师，从事中医心血管病临床研究，Tel: 025-52276242，E-mail: tcmantichf@126.com
- 基金信息：
  
  国家自然科学基金面上项目(81273716);江苏省“六大人才高峰”资助项目(WSN-067);南京市医学科技发展项目(YKK15119)
- DOI：10.13422/j.cnki.syfjx.20190336
  中图分类号： R2-0;R22;R285.5
- 收稿日期：2018-07-09，
  
  网络出版日期：2018-11-16，
  
  纸质出版日期：2019-02-05
- 稿件说明：
移动端阅览
刘学谦, 王静, 曹守沛, 等. 凉血散瘀法通过抑制巨噬细胞凋亡抗动脉粥样硬化的作用[J]. 中国实验方剂学杂志, 2019,25(3):59-65.

Xue-qian LIU, Jing WANG, Shou-pei CAO, et al. Effect of Cooling Blood Method in Inhibiting Macrophage Apoptosis Against Atherosclerosis[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(3): 59-65.
刘学谦, 王静, 曹守沛, 等. 凉血散瘀法通过抑制巨噬细胞凋亡抗动脉粥样硬化的作用[J]. 中国实验方剂学杂志, 2019,25(3):59-65. DOI： 10.13422/j.cnki.syfjx.20190336.

Xue-qian LIU, Jing WANG, Shou-pei CAO, et al. Effect of Cooling Blood Method in Inhibiting Macrophage Apoptosis Against Atherosclerosis[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(3): 59-65. DOI： 10.13422/j.cnki.syfjx.20190336.

摘要

目的:

观察凉血散瘀法清心通脉饮含药血清对乙酰化低密度脂蛋白(acetylated low density lipoprotein

ac-LDL)诱导的小鼠单核巨噬细胞系RAW264.7凋亡率及A型清道夫受体(type A scavenger receptor

SR-A)，B细胞淋巴瘤-2(B-cell lymphoma-2，Bcl-2)，Bcl-2相关X蛋白(Bcl-2-associated X protein

Bax)，肌醇需要酶1

(inositol-requiring enzyme l

，IRE1

)表达的影响，探讨清心通脉饮治疗动脉粥样硬化可能的作用机制。

方法:

8只新西兰兔采用随机数字法分为阿托伐他汀组(2.6 g·kg

-1

)，清心通脉饮低、中、高剂量组(3.33，6.66，13.32 mg·kg

-1

)，灌胃7 d后颈动脉采血收集含药血清。各组用2.5，5，10，20%体积分数的含药血清培养液分别刺激RAW264.7细胞系6，12，24 h，采用细胞增殖与活性检测-8(CCK-8)法观察细胞增殖率。体外培养RAW264.7细胞系，分为空白组、模型组、阿托伐他汀组、清心通脉饮低、中、高剂量组。空白组用牛血清白蛋白(BSA)培养细胞，模型组用BSA+ 50 mg·L

-1

ac-LDL刺激细胞24 h，其他组用BSA+ 50 mg·L

-1

ac-LDL+ 10%含药血清刺激细胞24 h。流式细胞技术检测每组RAW264.7细胞系凋亡率和SR-A的表达，蛋白免疫印迹法(Western blot)检测Bcl-2，Bax

IRE1

蛋白的表达。

结果:

与空白组比较，模型组可显著增加RAW264.7细胞凋亡率(

0.01)，并增加Bax

SR-A蛋白表达(

0.01)，减少Bcl-2蛋白表达(

0.05)。与模型组比较，清心通脉饮低、中、高剂量组均可降低RAW264.7细胞系凋亡率(

0.05)，减少SR-A和IRE1

表达(

0.05，

0.01)。清心通脉饮低、高剂量组可降低Bax表达(

0.05，

0.01)；清心通脉饮中、高剂量组可降低Bcl-2表达(

0.05)。

结论:

清心通脉饮可降低巨噬细胞凋亡率，其治疗动脉粥样硬化机制可能与调控相关凋促亡蛋白Bax

IRE

，SR-A和抗凋亡蛋白Bcl-2的表达有关。

Abstract

Objective:

To observe the effect of serum-containing Qingxin Tongmai decoction(QXTMD) on the apoptosis rate of mouse mononuclear macrophage cell line RAW264.7 induced by Acetylated low density lipoprotein (ac-LDL) and the expressions of type A scavenger receptor(SR-A)

B-cell lymphoma-2(Bcl-2)

Bcl-2-associated X protein(Bax)

inositol-requiring enzyme 1

(IRE1

)

exploring the possible mechanism of QXTMD in the treatment of atherosclerosis.

Method:

Eight New Zealand rabbits were randomly divided into the atorvastatin group (2.6 g·kg

-1

) low

medium and high-dose QXTMD groups (3.33

6.66

13.32 mg·kg

-1

). After 7 days of gavage

the carotid blood was collected to prepare drug-containing serum. The RAW264.7 cell line was stimulated with 2.5%

10%

and 20%drug-containing serum culture for 6

and 24 h

respectively. The cell proliferation rate was observed by cell counting kit-8 (CCK-8) method. The RAW264.7 cell line was cultured

in vitro

and divided into blank group

model group

atorvastatin group

and low

medium and high-dose QXTMY groups. The cells in blank group were cultured with bovine serum albumin(BSA). The model group was stimulated with BSA+ 50 mg·L

-1

ac-LDL for 24 h. The other groups were stimulated with BSA+ 50 mg·L

-1

ac-LDL+ 10%drug-containing serum for 24 h. The apoptosis rate and SR-A expression of RAW264.7 cells were detected by flow cytometry. The expressions of Bcl-2

Bax and IRE1

protein were detected by Western blot.

Result:

Compared with the blank group

the model group could increase the apoptosis rate of RAW264.7 cells (

0.01) and the expressions of Bax and SR-A protein (

0.01)

but decrease the expression of Bcl-2 protein (

0.05). Compared with the model group

low

medium and high-dose QXTMD groups could decrease the apoptosis rate of RAW264.7 cell line (

0.05) and the expressions of SR-A and IRE1

(

0.05

0.01). The low-dose QXTMD group and the high-dose QXTMD group could decrease the expression of Bax(

0.05

0.01). The middle-dose group and the high-dose group could decrease the expression of Bcl-2(

0.01).

Conclusion:

QXTMD can reduce the apoptosis rate of macrophages. The mechanism of atherosclerosis may be related to the expressions of Bax

IRE

SR-A and anti-apoptotic protein Bcl-2.

关键词

Keywords

references

陈伟伟，高润霖，刘力生，等 . 《中国心血管病报告2017》概要 [J]. 中国循环杂志， 2018 , 33 ( 1 ): 1 - 8 .

Perrotta P , Veseli B E , Van der Veken B , et al . Pharmacological strategies to inhibit intra-plaque angiogenesis in atherosclerosis [J]. Vascul Pharmacol , 2018 , doi: 10.1016/j.vph.2018.06.014 doi:10.1016/j.vph.2018.06.014 .

Andres V , Pello O M , Silvestre-Roig C. Macrophage proliferation and apoptosis in atherosclerosis [J]. Curr Opin Lipidol , 2012 , 23 ( 5 ): 429 - 438 .

Orekhov A N . LDL and foam cell formation as the basis of atherogenesis [J]. Curr Opin Lipidol , 2018 , 29 ( 4 ): 279 - 284 .

Gonzalez L , Trigatti B L. Macrophage apoptosis and necrotic core development in atherosclerosis: a rapidly advancing field with clinical relevance to imaging and therapy [J]. Can J Cardiol , 2017 , 33 ( 3 ): 303 - 312 .

殷小杰，马晓静，王岚，等 . 三黄泻心汤活血化瘀优势方抗动脉粥样硬化的作用机制 [J]. 中国实验方剂学杂志， 2018 , 24 ( 22 ): 83 - 88 .

陈宁，宋囡，贾连群，等 . 化瘀祛痰方对AS家兔肝脏线粒体呼吸链酶复合物的影响 [J]. 中国实验方剂学杂志， 2018 , 24 ( 7 ): 171 - 176 .

周仲瑛 . 瘀热相搏证的系列研究（一） [J]. 天津中医药大学学报， 2008 , 27 ( 3 ): 151 - 155 .

刘美之，郎艳松，张鑫月，等 . 从痰、瘀、毒论治动脉粥样硬化研究进展 [J]. 中医杂志， 2014 , 55 ( 9 ): 800 - 803 .

孙少卫，童文娟，谢雪娇，等 . 动脉粥样硬化的中西医观 [J]. 中国动脉硬化杂志， 2016 , 24 ( 5 ): 524 - 528 .

钟伟，王永刚，于远望，等 . 中医防治颈动脉粥样硬化的研究进展 [J]. 中华中医药学刊， 2017 , 35 ( 8 ): 2043 - 2045 .

伦琦星，刘炳琳，李军，等．猫耳刺皂苷ilexpernoside C抑制低密度脂蛋白多聚体诱导泡沫细胞形成的活性及机制研究 [J]. 中国中药杂志， 2016 , 41 ( 3 ): 498 - 503 .

Kzhyshkowska J , Neyen C , Gordon S. Role of macrophage scavenger receptors in atherosclerosis [J]. Immunobiology , 2012 , 217 ( 5 ): 492 - 502 .

Tsuzuki S , Kimoto Y , Lee S , et al . A novel role for scavenger receptor B1 as a contributor to the capture of specific volatile odorants in the nasal cavity [J]. Biomed Res , 2018 , 39 ( 3 ): 117 - 129 .

ZHU G Y , ZHU X L , LI R T , et al . Atorvastatin inhibits scavenger receptor A and monocyte chemoattractant protein-1 expressions in foam cell [J]. Chin J Cardiol Med , 2007 , 35 ( 7 ): 666 - 669 .

DAI X Y , CAI Y , MAO D D , et al . Increased stability of phosphatase and tensin homolog by intermedin leading to scavenger receptor A inhibition of macrophages reduces atherosclerosis in apolipoprotein E-deficient mice [J]. J Mol Cell Cardiol , 2012 , 53 ( 4 ): 509 - 520 .

To M , Peterson C W , Roberts M A , et al . Lipid disequilibrium disrupts ER proteostasis by impairing ERAD substrate glycan trimming and dislocation [J]. Mol Biol Cell , 2017 , 28 ( 2 ): 270 - 284 .

Abdullah A , Ravanan P. The unknown face of IRE1 alpha-Beyond ER stress [J]. Eur J Cell Biol , 2018 , 97 ( 5 ): 359 - 368 .

刘斯文，郭晓辰，张军平 . 内质网应激中IRE1级联反应对动脉粥样硬化的作用 [J]. 中国病理生理杂志， 2016 , 32 ( 6 ): 1147 - 1152 .

ZHOUA X , Tabas I. The UPR in atherosclerosis [J]. Semin Immunopathol , 2013 , 35 ( 3 ): 321 - 332 .

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

基于NLRP3炎症小体介导的巨噬细胞焦亡探究黄芩-黄连对动脉粥样硬化的干预机制

内质网应激在动脉粥样硬化中的作用及中医药调控研究进展

艳山姜挥发油通过调控巨噬细胞CD36和ABCA1表达抑制泡沫细胞的形成

补阳还五汤对LPS诱导巨噬细胞活化与自噬的影响