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

doi:10.12998/wjcc.v8.i10.1848

Cross electro-nape-acupuncture ameliorates cerebral hemorrhage-induced brain damage by inhibiting necroptosis

World J Clin Cases. 2020 May 26;8(10):1848-1858. doi: 10.12998/wjcc.v8.i10.1848.

Authors

Guo-Feng Cai¹, Zhong-Ren Sun², Zhe Zhuang³, Hai-Chun Zhou¹, Shan Gao⁴, Kai Liu¹, Li-Li Shang³, Kun-Ping Jia⁵, Xiu-Zhen Wang¹, Hui Zhao³, Guo-Liang Cai⁶, Wen-Li Song⁶, Sheng-Nan Xu⁷

Affiliations

¹ Hanan Branch of Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin 150001, Heilongjiang Province, China.
² Heilongjiang University of Traditional Chinese Medicine, Harbin 150040, Heilongjiang Province, China.
³ Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin 150000, Heilongjiang Province, China.
⁴ First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin 150040, Heilongjiang Province, China.
⁵ Hanan Branch of Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin 150001, Heilongjiang Province, China. jka3ih@163.com.
⁶ Harbin Sport University, Harbin 150001, Heilongjiang Province, China.
⁷ Graduate School of Heilongjiang University of Traditional Chinese Medicine, Harbin 150040, Heilongjiang Province, China.

Abstract

Background: Receptor interacting protein kinase 1 (RIPK1)-mediated cell death, including apoptosis and necroptosis, belongs to programmed cell death. It has been reported that RIPK1-mediated necroptosis exists in lesions of cerebral hemorrhage (CH). Electroacupuncture, a treatment derived from traditional Chinese medicine, could improve neurological impairment in patients with brain injury.

Aim: To investigate the protective role of cross electro-nape acupuncture (CENA) in CH, and clarify the potential mechanism.

Methods: CH rat models were established, and CENA was applied to the experimental rats. Neurological functions and encephaledema were then measured. Necrotic cells in the brain of rats with CH were evaluated by propidium iodide staining. Necroptosis was assessed by immunofluorescence. Activation of the necroptosis-related pathway was detected by western blot. Extraction of brain tissue, cerebrospinal fluid and serum samples was conducted to measure the expression and secretion of inflammatory cytokines by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay.

Results: The necroptotic marker p-MLKL was detectable in the brains of rats with CH. Next, we found that CENA could ameliorate neurological functions in rat models of CH. Moreover, the upregulation of RIPK1-mediated necroptosis-related molecules in the brains of rats with CH were inhibited by CENA. Further investigation revealed that CENA partially blocked the interaction between RIPK1 and RIPK3. Finally, in vivo assays showed that CENA decreased the expression of the inflammatory cytokines tumor necrosis factor-α, interleukin-6 and interleukin-8 in CH rat models.

Conclusion: These findings revealed that CENA exerts a protective role in CH models by inhibiting RIPK1-mediated necroptosis.

Keywords: Cerebral hemorrhage; Cross electro-nape acupuncture; Enzyme-linked immunosorbent assay; Necroptosis; Quantitative real-time polymerase chain reaction; Receptor interacting protein kinase 1.