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

许骞; 刘力源; 张荣贤; 余芝; 郝锋; 张建斌

doi:10.13703/j.0255-2930.20230510-k0003

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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

机制探讨 | 更新时间：2024-06-03

- 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
- 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
- 中国针灸 2024年44卷第4期页码：433-440
- 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：
  
  许骞，南京中医药大学博士研究生。E-mail：871691898@qq.com
  张建斌，教授。E-mail：zhangjianbin@njucm.edu.cn
- 基金信息：
  
  国家自然科学基金资助项目(81973947)
- DOI：10.13703/j.0255-2930.20230510-k0003
  中图分类号：
- 收稿：2023-05-10，
  
  网络首发：2023-10-18，
  
  纸质出版：2024-04-12
- 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

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