Effects of moxibustion with wheat-grain size cone at "Zusanli" (ST 36) on vascular injury and oxidative stress in high-fat diet rats through mTOR/HIF-1α/VEGF signaling pathway

XU Qian; LIU Liyuan; ZHANG Rongxian; YU Zhi; HAO Feng; ZHANG Jianbin

doi:10.13703/j.0255-2930.20230510-k0003

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Effects of moxibustion with wheat-grain size cone at "Zusanli" (ST 36) on vascular injury and oxidative stress in high-fat diet rats through mTOR/HIF-1α/VEGF signaling pathway

Study on Mechanism | 更新时间：2024-06-03

- Effects of moxibustion with wheat-grain size cone at "Zusanli" (ST 36) on vascular injury and oxidative stress in high-fat diet rats through mTOR/HIF-1α/VEGF signaling pathway
- Chinese Acupuncture & Moxibustion Vol. 44, Issue 4, Pages: 433-440(2024)
- 作者机构：
  
  1.南京中医药大学第二附属医院/江苏省第二中医院针灸科，南京210017
  2.南京中医药大学针药结合教育部重点实验室
  3.南京中医药大学针灸推拿学院
- 作者简介：
- 基金信息：
- DOI：10.13703/j.0255-2930.20230510-k0003
  CLC：
- Received：10 May 2023，
  
  Online First：18 October 2023，
  
  Published：12 April 2024
- 稿件说明：
移动端阅览
许骞,刘力源,张荣贤,等.基于mTOR/HIF-1α/VEGF信号通路探讨麦粒灸“足三里”对高脂饮食大鼠血管损伤和氧化应激的影响[J].中国针灸,2024,44(4):433-440.

XU Qian,LIU Liyuan,ZHANG Rongxian,et al.Effects of moxibustion with wheat-grain size cone at "Zusanli" (ST 36) on vascular injury and oxidative stress in high-fat diet rats through mTOR/HIF-1α/VEGF signaling pathway[J].Chinese Acupuncture & Moxibustion,2024,44(04):433-440.
许骞,刘力源,张荣贤,等.基于mTOR/HIF-1α/VEGF信号通路探讨麦粒灸“足三里”对高脂饮食大鼠血管损伤和氧化应激的影响[J].中国针灸,2024,44(4):433-440. DOI： 10.13703/j.0255-2930.20230510-k0003.

XU Qian,LIU Liyuan,ZHANG Rongxian,et al.Effects of moxibustion with wheat-grain size cone at "Zusanli" (ST 36) on vascular injury and oxidative stress in high-fat diet rats through mTOR/HIF-1α/VEGF signaling pathway[J].Chinese Acupuncture & Moxibustion,2024,44(04):433-440. DOI： 10.13703/j.0255-2930.20230510-k0003.

摘要

目的

基于哺乳动物雷帕霉素靶蛋白（mTOR）/缺氧诱导因子-1α（HIF-1α）/血管内皮生长因子（VEGF）信号通路探讨麦粒灸“足三里”改善高脂血症血管损伤及氧化应激的效应机制。

方法

将40只健康SPF级雄性SD大鼠随机分为正常组、模型组、艾灸组和抑制剂组，每组10只。模型组、艾灸组、抑制剂组大鼠采用高脂饲料喂养8周建立高脂血症模型。艾灸组与抑制剂组于双侧“足三里”行麦粒灸干预，每次每穴灸3壮，每日1次，共4周。抑制剂组在每次麦粒灸干预前腹腔注射雷帕霉素溶液（2.0 mg/kg）。分别于造模后及干预后采用ELISA法检测大鼠血清总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）和低密度脂蛋白胆固醇（LDL-C）含量。于干预后采用HE染色、油红O染色观察大鼠腹主动脉形态及周围脂质沉积；分别采用WST-1、TBA和微板法检测血清超氧化物歧化酶（SOD）活性及丙二醛（MDA）、一氧化氮（NO）含量；Western blot法检测大鼠腹主动脉mTOR、HIF-1α、VEGF蛋白表达。

结果

造模后，与正常组比较，模型组、艾灸组、抑制剂组大鼠血清TC、TG、LDL-C含量升高（

0.01），HDL-C含量降低（

0.01）。干预后，与正常组比较，模型组大鼠血清TC、TG、LDL-C、MDA含量升高（

0.01），HDL-C含量、SOD活性及NO含量降低（

0.01）；腹主动脉组织细胞结构异常、周围脂质沉积较多；腹主动脉mTOR、HIF-1α、VEGF蛋白表达升高（

0.01，

0.05）。与模型组比较，艾灸组和抑制剂组大鼠血清TC、TG、LDL-C、MDA含量降低（

0.01），HDL-C含量、SOD活性及NO含量升高（

0.01，

0.05）；腹主动脉mTOR、HIF-1α、VEGF蛋白表达升高（

0.01，

0.05）；艾灸组血管组织结构改善、脂质沉积减少，抑制剂组血管组织结构异常、脂质沉积减少。与抑制剂组比较，艾灸组大鼠血清SOD活性、NO含量升高（

0.05），MDA含量降低（

0.05）；腹主动脉mTOR、HIF-1α、V

EGF蛋白表达升高（

0.01，

0.05）。

结论

麦粒灸“足三里”可通过改善氧化应激进而修复高脂饮食导致的血管损伤，其机制与调控mTOR/HIF-1α/VEGF信号通路有关。

Abstract

Objective

To explore the effect mechanism of moxibustion with wheat-grain size cone at "Zusanli" (ST 36) on vascular injury and oxidative stress in hyperlipidemia through mammalian target of rapamycin (mTOR)/hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) signaling pathway.

Methods

Forty healthy male SD rats with SPF grade were randomly divided into a normal group

a model group

a moxibustion group

and an inhibitor group

with 10 rats in each one. The hyperlipidemia model was established by feeding a high-fat diet for 8 weeks in rats of the model group

the moxibustion group and the inhibitor group. The moxibustion with wheat-grain size cone was delivered at bilateral "Zusanli" (ST 36) of each rat in the moxibustion group and the inhibitor group

with 3 cones on each acupoint in each intervention

once daily for 4 weeks. In the inhibitor group

before each intervention with moxibustion

rapamycin solution was injected intraperitoneally

2.0 mg/kg. After modeling and intervention

using ELISA

the levels of total cholesterol (TC)

triglyceride (TG)

high-density lipoprotein cholesterol (HDL-C)

and low-density lipoprotein cholesterol (LDL-C) in the serum of rats were determined. After intervention

with HE staining and oil red O staining adopted

the abdominal aortic morphology and peripheral lipid deposition were observed. Separately

using WST-1

TBA and micro-plate method

the superoxide dismutase (SOD) activity and the levels of malondialdehyde (MDA) and nitric oxide (NO) in the serum were detected. The protein expression of mTOR

HIF-1α and VEGF in abdominal aorta were measured by Western blot method.

Results

Compared with those in the normal group

the level

s of TC

TG and LDL-C increased (

0.01) and HDL-C decreased (

0.01) in the serum of the rats in the model group

the moxibustion group and the inhibitor group after model establishment. When compared with the normal group after intervention

in the model group

the serum levels of TC

LDL-C and MDA increased (

0.01)

HDL-C level

SOD activity and NO level were reduced (

0.01); the cell structure of the abdominal arota was abnormal

the peripheral lipids deposited seriously; and the protein expression of mTOR

HIF-1α and VEGF of abdominal aorta was elevated (

0.01

0.05). In comparison with the model group

the levels of TC

LDL-C and MDA were reduced (

0.01)

HDL-C levels

SOD activities and NO levels elevated (

0.01

0.05)

as well as the protein expression of mTOR

HIF-1α and VEGF of abdominal aorta (

0.01

0.05) in the moxibustion group and the inhibitor group; besides

the vascular structure was ameliorated and the lipid deposition reduced in the moxibustion group

while

the vascular structure was still abnormal and the lipid deposition declined in the inhibitor group. When compared with the inhibitor group

the serum SOD activity and NO level increased (

0.05) and MDA decreased (

0.05); and the protein expression of mTOR

HIF-1α and VEGF of abdominal aorta was elevated (

0.01

0.05) in the moxibustion group.

Conclusion

The vascular injury due to hyperlipidemia is repaired by moxibustion with wheat-grain size cone at "Zusanli" (ST 36) through ameliorating oxidative stress

which is associated potentially with the modulation of mTOR/HIF-1α/VEGF signaling pathway.

关键词

Keywords

references

Kaminsky LA , German C , Imboden M , et al . The importance of healthy lifestyle behaviors in the prevention of cardiovascular disease [J ] . Prog Cardiovasc Dis , 2022 , 70 : 8 - 15 .

中国心血管健康与疾病报告编写组 . 中国心血管健康与疾病报告2021概要 [J ] . 心脑血管病防治 , 2022 , 22 ( 4 ): 20 - 36, 40 .

黄志文 , 黄丽嫦 . 血管内皮细胞功能与冠心病缺血急性发作的相关性分析 [J ] . 当代医学 , 2020 , 26 ( 14 ): 39 - 41 .

Wang YR , Song XJ , Li ZB , et al . Long non-coding RNAs in coronary atherosclerosis [J ] . Life Sci , 2018 , 211 : 189 - 197 .

Kim YW , Byzova TV . Oxidative stress in angiogenesis and vascular disease [J ] . Blood , 2014 , 123 ( 5 ): 625 - 631 .

李梦醒 , 王玉 , 李真 , 等 . 基于miR-126-3p调控mTOR/HIF-1α信号通路探讨电针促脑缺血大鼠血管新生的机制 [J ] . 针刺研究 , 2022 , 47 ( 9 ): 749 - 758 .

高建芸 , 王桂英 , 王玲玲 . TRPV1介导不同温度艾灸调脂通脉效应的临床研究 [J ] . 时珍国医国药 , 2015 , 26 ( 9 ): 2182 - 2184 .

陆成轩 , 许骞 , 叶儒琳 , 等 . 45℃艾灸“足三里”改善高脂血症大鼠血管内皮的氧化应激 [J ] . 针刺研究 , 2023 , 48 ( 4 ): 331 - 338 .

王玲玲 . 麦粒灸临床特点及适宜病症 [J ] . 上海针灸杂志 , 2013 , 32 ( 11 ): 889 - 891 .

邵清华 , 李怡 . 麦粒灸治疗高脂血症临床观察 [J ] . 河南中医 , 2018 , 38 ( 9 ): 1400 - 1402 .

张细柳 , 王士超 , 王耀帅 , 等 . 不同灸量麦粒灸调节血脂效应的比较研究 [J ] . 中医杂志 , 2011 , 52 ( 5 ): 413 - 415 .

Bunbupha S , Apaijit K , Maneesai P , et al . Nobiletin ameliorates high-fat diet-induced vascular and renal changes by reducing inflammation with modulating AdipoR1 and TGF-β1 expression in rats [J ] . Life Sci , 2020 , 260 : 118398 .

中国针灸学会 . 实验动物常用穴位名称与定位第2部分:大鼠 [J ] . 针刺研究 , 2021 , 46 ( 4 ): 351 - 352 .

苏晓英 , 周飞仁 , 都跃 . 重复异丙酚麻醉通过mTOR通路诱导大鼠海马细胞凋亡及自噬 [J ] . 中国老年学杂志 , 2023 , 43 ( 2 ): 481 - 486 .

Xu R , Lin J , Zhao GQ , et al . Production of interleukin-1β related to mammalian target of rapamycin/Toll-like receptor 4 signaling pathway during Aspergillus fumigatus infection of the mouse cornea [J ] . Int J Ophthalmol , 2018 , 11 ( 5 ): 712 - 718 .

石宏 , 杨兆坤 , 王晓宇 , 等 . 电针中脘穴对大鼠胃内酸刺激诱导的胃伤害性反应的影响及其机制研究 [J ] . 中医杂志 , 2024 , 65 ( 2 ): 213 - 218 .

Forman HJ , Zhang HQ . Targeting oxidative stress in disease: promise and limitations of antioxidant therapy [J ] . Nat Rev Drug Discov , 2021 , 20 ( 9 ): 689 - 709 .

Cui CM , Li YH , Liu Y . Down-regulation of miR-377 suppresses high glucose and hypoxia-induced angiogenesis and inflammation in human retinal endothelial cells by direct up-regulation of target gene SIRT1 [J ] . Hum Cell , 2019 , 32 ( 3 ): 260 - 274 .

卢丹丹 , 赵静 , 任雷鸣 . 缺氧及血管周围神经改变对心脑血管的影响 [J ] . 神经药理学报 , 2014 , 4 ( 4 ): 28 - 35 .

Zhao M , Wang ST , Zuo AN , et al . HIF-1α/JMJD1A signaling regulates inflammation and oxidative stress following hyperglycemia and hypoxia-induced vascular cell injury [J ] . Cell Mol Biol Lett , 2021 , 26 ( 1 ): 40 .

Hurtubise J , McLellan K , Durr K , et al . The different facets of dyslipidemia and hypertension in atherosclerosis [J ] . Curr Atheroscler Rep , 2016 , 18 ( 12 ): 82 .

李文毅 , 周春阳 . 高脂血症与动脉粥样硬化和脂代谢研究进展 [J ] . 中国药理学与毒理学杂志 , 2019 , 33 ( 10 ): 811 .

魏红沁 , 丁春华 , 张晴 , 等 . 艾灸治疗高脂血症临床观察 [J ] . 上海针灸杂志 , 2009 , 28 ( 12 ): 698 - 699 .

张建斌 , 王玲玲 , 吴焕淦 , 等 . 艾灸温通温补概念的内涵分析 [J ] . 中国针灸 , 2012 , 32 ( 11 ): 1000 - 1003 .

黄凯裕 , 梁爽 , 孙征 , 等 . 艾灸温通效应的启动机制分析 [J ] . 中国针灸 , 2017 , 37 ( 9 ): 1023 - 1026 .

黄凯裕 , 梁爽 , 胡光勇 , 等 . 局部热刺激的生物学效应与艾灸温通原理 [J ] . 针刺研究 , 2015 , 40 ( 6 ): 504 - 509 .

陈仲杰 , 吴中朝 , 王京京 , 等 . 辨证施灸治疗高脂血症49例临床观察 [J ] . 中医杂志 , 2015 , 56 ( 22 ): 1935 - 1938 .

苏方方 , 高建芸 , 王桂英 , 等 . 45℃艾灸对高脂血症大鼠血脂及血清ox-LDL、NO的影响 [J ] . 中国针灸 , 2019 , 39 ( 2 ): 180 - 184 .

许骞 , 陆成轩 , 吴奂汐 , 等 . 不同灸程45℃“足三里”温和灸对高脂血症大鼠腹主动脉炎性因子的影响 [J ] . 针刺研究 , 2023 , 48 ( 9 ): 923 - 932 .

王晓彤 , 王欣欣 , 董闯 , 等 . 中医康复技术操作规范·麦粒灸 [J ] . 康复学报 , 2022 , 32 ( 2 ): 100 - 105 .

Xu Q , Wu HX , Zhu HB , et al . Grain-sized moxibustion at Zusanli (ST36) promotes hepatic autophagy in rats with hyperlipidemia by regulating the ULK1 and TFEB expression through the AMPK/mTOR signaling pathway [J ] . Heliyon , 2023 , 9 ( 5 ): e15316 .

郭炎峰 , 郭海海 , 范玉雪 , 等 . 苜蓿素对高脂饲粮诱发的大鼠血管内皮损伤的治疗作用 [J ] . 动物营养学报 , 2022 , 34 ( 10 ): 6768 - 6780 .

谢先龙 , 吴艳霞 , 吴婷玉 , 等 . 老年血管性痴呆患者认知功能与血清Hcy和SOD水平的关系 [J ] . 中国实用神经疾病杂志 , 2018 , 21 ( 14 ): 1537 - 1540 .

郭国庆 , 查彩慧 , 沈伟哉 . 一氧化氮与动脉粥样硬化的关系 [J ] . 心血管病学进展 , 2001 , 22 ( 3 ): 178 - 180 .

冯浩楼 , 黄海森 , 范新发 , 等 . 瓜蒌通脉丸对高脂血症大鼠血脂及血管NO、SOD、MDA的影响 [J ] . 医学研究与教育 , 2009 , 26 ( 6 ): 60 - 63 .

魏英杰 , 白媛媛 . 生物标志物与心力衰竭 [M ] . 北京 : 中国协和医科大学出版社 , 2017 .

林丽 , 唐朝枢 , 袁文俊 . 血管内皮的保护策略 [J ] . 国外医学(生理、病理科学与临床分册) , 2003 , 23 ( 4 ): 334 - 337 .

刘德培 . 中华医学百科全书基础医学, 人体生理学: 基础医学人体生理学 [M ] . 北京 : 中国协和医科大学出版社 , 2017 .

杨军珂 , 吴宗贵 , 郭延松 , 等 . 大鼠动脉粥样硬化和高脂血症一氧化氮特点的比较 [J ] . 上海医学 , 2003 , 26 ( 4 ): 239 - 242 .

强晟 , 朱德淳 , 张建斌 . 艾灸干预血管内皮细胞损伤作用机制研究进展 [J ] . 山西中医 , 2021 , 37 ( 3 ): 58 - 60 .

Ke QD , Costa M . Hypoxia-inducible factor-1 (HIF-1) [J ] . Mol Pharmacol , 2006 , 70 ( 5 ): 1469 - 1480 .

Yang C , Zhong ZF , Wang SP , et al . HIF-1: structure, biology and natural modulators [J ] . Chin J Nat Med , 2021 , 19 ( 7 ): 521 - 527 .

Kobayashi Y , Oguro A , Imaoka S . Feedback of hypoxia-inducible factor-1alpha (HIF-1alpha) transcriptional activity via redox factor-1 (Ref-1) induction by reactive oxygen species (ROS) [J ] . Free Radic Res , 2021 , 55 ( 2 ): 154 - 164 .

Pouysségur J , Mechta-Grigoriou F . Redox regulation of the hypoxia-inducible factor [J ] . Biol Chem , 2006 , 387 ( 10/11 ): 1337 - 1346 .

Reuter S , Gupta SC , Chaturvedi MM , et al . Oxidative stress, inflammation, and cancer: how are they linked? [J ] . Free Radic Biol Med , 2010 , 49 ( 11 ): 1603 - 1616 .

王超 , 刘薇薇 , 黄洁 , 等 . 不同艾灸预处理时间对心肌缺血再灌注损伤大鼠心肌细胞中HIF-1α、Bcl-2及Caspase-3表达的影响 [J ] . 中医药学报 , 2017 , 45 ( 4 ): 70 - 74 .

Nakahara T , Morita A , Yagasaki R , et al . Mammalian target of rapamycin (mTOR) as a potential therapeutic target in pathological ocular angiogenesis [J ] . Biol Pharm Bull , 2017 , 40 ( 12 ): 2045 - 2049 .

苑红 , 王晓娟 , 李存保 , 等 . 胰岛素抵抗小鼠中mTOR的表达 [J ] . 内蒙古医学杂志 , 2016 , 48 ( 4 ): 394 - 396 .

姚俊鹏 , 周思远 , 鄢香芸 , 等 . 基于mTOR/P70S6K信号通路探讨电针对肥胖大鼠脂肪组织自噬的影响 [J ] . 中华中医药杂志 , 2022 , 37 ( 5 ): 2633 - 2638 .

Ferrara N . VEGF and intraocular neovascularization: from discovery to therapy [J ] . Transl Vis Sci Technol , 2016 , 5 ( 2 ): 10 .

岑团 , 黄照河 , 刘燕 . 血管内皮生长因子与动脉粥样硬化斑块的研究进展 [J ] . 右江医学 , 2021 , 49 ( 6 ): 465 - 468 .

管媛媛 , 张宏如 , 张皓然 , 等 . 麦粒灸对自发性高血压大鼠血压及mTOR蛋白表达的影响 [J ] . 中西医结合心脑血管病杂志 , 2016 , 14 ( 4 ): 361 - 363 .

李庆羚 , 马强 , 李悦 , 等 . 艾灸对慢性心力衰竭大鼠心功能及心肌细胞自噬相关蛋白表达的影响 [J ] . 针刺研究 , 2020 , 45 ( 4 ): 259 - 263, 274 .

张皓然 , 张宏如 , 卢圣锋 , 等 . 逆灸对力竭运动大鼠心肌组织中AMPK、mTOR的影响 [J ] . 中国针灸 , 2017 , 37 ( 5 ): 521 - 526 .

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