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

Qian Yu; Shi Shu; Xin-Yao Ju; Wei Peng; Xue-Qi Ren; Shu-Han Si; Shi-Zhen Song; Xue-Yun Xie; Bang-Jiang Fang; Shuang Zhou

doi:10.1007/s11655-023-3715-z

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

Chin J Integr Med. 2024 Mar 27. doi: 10.1007/s11655-023-3715-z. Online ahead of print.

Authors

Qian Yu¹, Shi Shu², Xin-Yao Ju¹, Wei Peng³, Xue-Qi Ren², Shu-Han Si¹, Shi-Zhen Song¹, Xue-Yun Xie¹, Bang-Jiang Fang³, Shuang Zhou⁴

Affiliations

¹ School of Acupuncture-Moxibustion and Tuina, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
² College of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
³ Department of Emergency, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
⁴ School of Acupuncture-Moxibustion and Tuina, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. zhoushuang8008@163.com.

PMID: 38532151
DOI: 10.1007/s11655-023-3715-z

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.

Keywords: Shuigou (GV 26); acupuncture points; angiogenesis; cerebral ischemia; electroacupuncture; miRNA-7.