Skip to main content
SpringerLink
Log in

Electroacupuncture Promotes Angiogenesis in Mice with Cerebral Ischemia by Inhibiting miR-7

  • Acupuncture Research
  • Published:
Chinese Journal of Integrative Medicine Aims and scope Submit manuscript

Abstract

Objective

To observe the angiogenesis effect of electroacupuncture (EA) at Shuigou acupoint (GV 26) in the treatment of cerebral ischemia, and explore the value of miRNA-7 (miR-7) in it.

Methods

First, 48 mice were randomly divided into sham operation, middle cerebral artery occlusion (MCAO) model, and EA treatment groups. Then 9 mice were divided into carrier control group, miR-7 knockout group and miR-7 overexpression group (n=3 each group). Finally, 20 mice were divided into model and carrier control group, model and miR-7 knockout group, EA treatment and carrier control group and EA treatment and miR-7 overexpression group, with 3–6 mice in each group. The MCAO model was established in the MCAO and EA groups. Neurological deficit score and 2,3,5-triphenyltetrazolium chloride (TTC) staining were used to evaluate the severity of cerebral ischemia. Hematoxylin-eosin staining was used to describe basic pathological changes. Immunohistochemistry was used to quantify cerebral microvessel density. Real-time PCR and Western blot were used to detect the expression of miR-7 and its downstream target genes Krüppel-like factor 4/vascular endothelial growth factor (KLF4/VEGF) and angiopoietin-2 (ANG-2) in the ischemic cerebral cortex.

Results

After EA, neurological deficit scores and infarction volumes decreased, and the density of cerebral microvessels increased. In the MCAO group, miR-7 expression was higher than that in the sham group (P<0.01). After EA at GV 26, miR-7 expression decreased (P<0.01) and the expression of downstream target genes KLF4/VEGF and ANG-2 increased as compared with the MCAO group (P<0.01). After EA combined with overexpression of miR-7, the expression of downstream target genes KLF4/VEGF and ANG-2 decreased compared to the control EA group (P<0.01). After miR-7 knockdown, the expression of KLF4/VEGF and ANG-2 increased (P<0.05 or P<0.01).

Conclusions

EA could promote angiogenesis in MCAO mice likely by inhibiting the expression of miR-7 and relieving inhibition of downstream target genes KLF4/VEGF and ANG-2.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Availability of Data and Material

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Li YZ, Wen L, Wei X, Wang QR, Xu LW, Zhang HM, et al. Inhibition of miR-7 promotes angiogenesis in human umbilical vein endothelial cells by upregulating VEGF via KLF4. Oncol Rep 2016;36:1569–1575.

    Article  CAS  PubMed  Google Scholar 

  2. Belloni D, Marcatti M, Ponzoni M, Ciceri F, Veschini L, Corti A, et al. Angiopoietin-2 in bone marrow milieu promotes multiple myeloma-associated angiogenesis. Exp Cell Res 2015;330:1–12.

    Article  CAS  PubMed  Google Scholar 

  3. Zhu W, Ye Y, Liu Y, Wang XR, Shi GX, Zhang S, et al. mechanisms of acupuncture therapy for cerebral ischemia: an evidence-based review of clinical and animal studies on cerebral ischemia. J Neuroimmune Pharmacol 2017;12:575–592.

    Article  PubMed  Google Scholar 

  4. Russell WMS, Burch RL, eds. The principles of humane experimental technique. London: Methuen; 1959.

    Google Scholar 

  5. Hata R, Mies G, Wiessner C, Fritze K, Hesselbarth D, Brinker G, et al. A reproducible model of middle cerebral artery occlusion in mice: hemodynamic, biochemical, and magnetic resonance imaging. J Cereb Blood Flow Metab 1998;18:367–375.

    Article  CAS  PubMed  Google Scholar 

  6. Li CR, Hua XB, Song DL, Zhou HL, Hu YL. Commonly used acupuncture points in mice. Exp Anim Anim Exp (Chin) 1992;2:85–87.

    Google Scholar 

  7. Hunter AJ, Hatcher J, Virley D, Nelson P, Irving E, Hadingham SJ, et al. Functional assessments in mice and rats after focal stroke. Neuropharmacology 2000;39:806–816.

    Article  CAS  PubMed  Google Scholar 

  8. Benedek A, Móricz K, Jurányi Z, Gigler G, Lévay G, Hársing LG Jr, et al. Use of TTC staining for the evaluation of tissue injury in the early phases of reperfusion after focal cerebral ischemia in rats. Brain Res 2006;1116:159–165.

    Article  CAS  PubMed  Google Scholar 

  9. Weidner N, Semple JP, Welch WR, Folkman J. Tumor angiogenesis and metastasis—correlation in invasive breast carcinoma. N Engl J Med 1991;324:1–8.

    Article  CAS  PubMed  Google Scholar 

  10. Li J, Zhang M, He Y, Du YH, Zhang XZ, Georgi R, et al. Molecular mechanism of electroacupuncture regulating cerebral arterial contractile protein in rats with cerebral infarction based on MLCK pathway. Chin J Integr Med 2023;29:61–68.

    Article  CAS  PubMed  Google Scholar 

  11. Chen B, Lin WQ, Li ZF, Zhong XY, Wang J, You XF, et al. Electroacupuncture attenuates ischemic brain injury and cellular apoptosis via mitochondrial translocation of cofilin. Chin J Integr Med 2021;27:705–712.

    Article  CAS  PubMed  Google Scholar 

  12. Li J, Chen L, Li D, Lu M, Huang X, Han X, et al. Electroacupuncture promotes the survival of the grafted human MGE neural progenitors in rats with cerebral ischemia by promoting angiogenesis and inhibiting inflammation. Neural Plast 2021;2021:4894881.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Fu SP, He SY, Xu B, Hu CJ, Lu SF, Shen WX, et al. Acupuncture promotes angiogenesis after myocardial ischemia through H3K9 acetylation regulation at VEGF gene. PLoS One 2014;9:e94604.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Feng R, Zhang F. The neuroprotective effect of electroacupuncture against ischemic stroke in animal model: a review. Afr J Tradit Complement Altern Med 2014;11:25–29.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Abali AE, Cabioglu T, Bayraktar N, Ozdemir BH, Moray G, Haberal M. Efficacy of acupuncture on pain mechanisms, inflammatory responses, and wound healing in the acute phase of major burns: an experimental study on rats. J Burn Care Res 2022;43:389–398.

    Article  PubMed  Google Scholar 

  16. Hong H, Yue JM, Zhang WJ, Zhu BM. Epigenetic mechanisms of angiogenesis in the ischemic heart diseases with acupuncture treatment. Med Acupunct 2020;32:381–384.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Wu Y, Hu R, Zhong X, Zhang A, Pang B, Sun X, et al. Electric acupuncture treatment promotes angiogenesis in rats with middle cerebral artery occlusion through ephb4/ephrinb2 mediated Src/PI3K signal pathway. J Stroke Cerebrovasc Dis 2021;30:105165.

    Article  PubMed  Google Scholar 

  18. Chang SQ, Zhang XC, Zhang A, Song YY, Jiang SY, Zhang ZH, et al. Acupuncture intervention prolongates thrombolysis time window by regulating cerebral cortex angiogenesis-related genes and proteins in cerebral infarction rats. Acupunct Res (Chin) 2021;46:751–756.

    CAS  Google Scholar 

  19. Gu YH, Zhang XC, Xu WT, Zhang A, Zhang ZH, Jiang SY, et al. Effect of acupuncture on neurological function, cerebral infarction volume, thrombolysis time window and cerebral cell apoptosis signaling pathway in cerebral infarction rats. Acupunct Res (Chin) 2020;45:209–214.

    Google Scholar 

  20. Tang YL, Liu ML, Luo J, Li N, Zhang GS, Yu J, et al. Exploring the effect of acupuncture plus mild hypothermia on miRNA-204 and its target gene expressions in CIRI rat brain tissues based on MAPK signal pathway. J Acupunct Tuina Sci 2021;19:338–344.

    Article  Google Scholar 

  21. Shi L, Cao HM, Li Y, Xu SX, Zhang Y, Zhang Y, et al. Electroacupuncture improves neurovascular unit reconstruction by promoting collateral circulation and angiogenesis. Neural Regen Res 2017;12:2000–2006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Lin J, Liu Z, Liao S, Li E, Wu X, Zeng W. Elevated microRNA-7 inhibits proliferation and tumor angiogenesis and promotes apoptosis of gastric cancer cells via repression of Raf-1. Cell Cycle 2020;19:2496–2508.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Babae N, Bourajjaj M, Liu Y, Van Beijnum JR, Cerisoli F, Scaria PV, et al. Systemic miRNA-7 delivery inhibits tumor angiogenesis and growth in murine xenograft glioblastoma. Oncotarget 2014;5:6687–6700.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Fan X, Liu M, Tang H, Leng D, Hu S, Lu R, et al. MicroRNA-7 exerts antiangiogenic effect on colorectal cancer via ERK signaling. J Surg Res 2019;240:48–59.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Acupuncture-Moxibustion and Tuina, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China

    Qian Yu, Xin-yao Ju, Shu-han Si, Shi-zhen Song, Xue-yun Xie & Shuang Zhou

  2. College of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China

    Shi Shu & Xue-qi Ren

  3. Department of Emergency, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China

    Wei Peng & Bang-jiang Fang

Authors
  1. Qian Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shi Shu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xin-yao Ju
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wei Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xue-qi Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shu-han Si
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shi-zhen Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xue-yun Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Bang-jiang Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Shuang Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Zhou S and Shu S independently designed the study. Yu Q and Ju XY carried out the experiment. Yu Q, Peng W, Ren XQ, Si SH, Song SZ, Xie XY collected and analyzed the data. Yu Q wrote the initial draft of the paper. Shu S and Fang BJ assisted with refinement of the manuscript. All authors approved the final version of the paper.

Corresponding author

Correspondence to Shuang Zhou.

Ethics declarations

The authors confirm that there is no conflict of interest related to the manuscript.

Additional information

Supported by the National Natural Science Foundation of China (No. 81874505)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yu, Q., Shu, S., Ju, Xy. et al. Electroacupuncture Promotes Angiogenesis in Mice with Cerebral Ischemia by Inhibiting miR-7. Chin. J. Integr. Med. (2024). https://doi.org/10.1007/s11655-023-3715-z

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11655-023-3715-z

Keywords

Search

Navigation