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©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
Cross electro-nape-acupuncture ameliorates cerebral hemorrhage-induced brain damage by inhibiting necroptosis
Guo-Feng Cai, Zhong-Ren Sun, Zhe Zhuang, Hai-Chun Zhou, Shan Gao, Kai Liu, Li-Li Shang, Kun-Ping Jia, Xiu-Zhen Wang, Hui Zhao, Guo-Liang Cai, Wen-Li Song, Sheng-Nan Xu
Guo-Feng Cai, Hai-Chun Zhou, Kai Liu, Kun-Ping Jia, Xiu-Zhen Wang, Hanan Branch of Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin 150001, Heilongjiang Province, China
Guo-Feng Cai, Postdoctoral Research Station of Heilongjiang Academy of Traditional Chinese Medicine, Harbin 150001, Heilongjiang Province, China
Zhong-Ren Sun, Heilongjiang University of Traditional Chinese Medicine, Harbin 150040, Heilongjiang Province, China
Zhe Zhuang, Li-Li Shang, Hui Zhao, Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin 150000, Heilongjiang Province, China
Shan Gao, First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin 150040, Heilongjiang Province, China
Guo-Liang Cai, Wen-Li Song, Harbin Sport University, Harbin 150001, Heilongjiang Province, China
Sheng-Nan Xu, Graduate School of Heilongjiang University of Traditional Chinese Medicine, Harbin 150040, Heilongjiang Province, China
Author contributions: Cai GF, Xu SN, Sun ZR and Zhuang Z performed the majority of experiments and analyzed the data; Zhou HC and Gao S performed the molecular investigations; Liu K, Shang LL and Jia KP designed and coordinated the research; Wang XZ, Zhao H, Cai GL and Song WL wrote the paper; Cai GF and Sun ZR contributed equally to this work.
Supported by State Administration of Traditional Chinese Medicine of Heilongjiang Province, No. ZHY16-027; and Harbin Municipal Science and Technology Bureau-Youth Reserve Talent Project, No. 2017RAQXJ170.
Institutional animal care and use committee statement: This study was reviewed and approved by the Animal Use and Care Committee of Heilongjiang University of Chinese Medicine.
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Kun-Ping Jia, MSc, Attending Doctor, Hanan Branch of Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, No. 26, Second Avenue, Pingfang District, Harbin 150001, Heilongjiang Province, China. jka3ih@163.com
Received: January 10, 2020
Peer-review started: January 10, 2020
First decision: February 20, 2020
Revised: March 1, 2020
Accepted: April 22, 2020
Article in press: April 22, 2020
Published online: May 26, 2020
ARTICLE HIGHLIGHTS
Research background
Cerebral hemorrhage (CH) is a severe disease worldwide. Although accumulating evidence has demonstrated that cell death is the dominant event in the pathogenesis of CH, there is still a lack of preferred treatment. Therefore, developing novel methods to treat CH is currently an urgent issue.
Research motivation
Our previous study showed that cross electro-nape acupuncture (CENA), a modified electroacupuncture, could ameliorate lung infection in patients with CH. However, the role of CENA in brain damage in patients with CH and the underlying mechanism are still unclear.
Research objectives
The aim of this work was to investigate the exact effect of CENA on rats with CH and its underlying mechanism.
Research methods
Rats were surgically treated to mimic CH and received CENA treatment. Propidium iodide staining and immunofluorescence analysis were performed to determine cell death. Neurological score, behavioral score and brain water content were calculated to evaluate brain damage. Western blot, immunoprecipitation assay, quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay were conducted to determine the underlying mechanism.
Research results
The present study identified the presence of necroptotic marker p-MLKL in the brain tissues of rats with CH. CENA decreased neurological score, behavioral score and brain water content in rats with CH. Further investigation revealed that CENA inhibited necrosome formation and the expression of IL-6, IL-8 and TNF-α in rats with CH.
Research conclusions
Our research found that receptor interacting protein kinase 1 (RIPK1)-mediated necroptosis was involved in brain damage in rats with CH. CENA treatment suppressed necroptosis and the inflammatory response to ameliorate brain damage in rats with CH, providing a novel strategy for CH treatment.
Research perspectives
Based on the clinical findings and in vivo experiments, RIPK1 could be a novel therapeutic target for CH-induced brain damage, and CENA improved brain damage by targeting RIPK1 and inhibiting the expression of inflammatory factors. Further in vivo assays in primates are necessary to clarify the protective effects of CENA on CH-induced brain damage, which is very meaningful and would contribute to the clinical application of CENA.
