Jisuikang formula promotes spinal cord injury repair in rats by activating the YAP/PKM2 signaling axis in astrocytes
10.12122/j.issn.1673-4254.2024.04.03
- VernacularTitle:脊髓康通过激活星形胶质细胞的YAP/PKM2信号轴促进脊髓损伤大鼠神经功能的恢复
- Author:
Hao MAN
1
,
2
;
Jianwei WANG
;
Mao WU
;
Yang SHAO
;
Junfeng YANG
;
Shaoshuo LI
;
Jinye LÜ
;
Yue ZHOU
Author Information
1. 南京中医药大学,江苏 南京 210023
2. 无锡市中医医院,江苏 无锡 214071
- Keywords:
spinal cord injury;
astrocytes;
aerobic glycolysis;
Jisuikang formula;
PKM2;
YAP
- From:
Journal of Southern Medical University
2024;44(4):636-643
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of Jisuikang formula-medicated serum for promoting spinal cord injury (SCI) repair in rats and explore the possible mechanism. Methods Thirty adult SD rats were randomized into sham-operated group, SCI (induced using a modified Allen method) model group, and Jisuikang formula-medicated serum treatment group. After the operations, the rats were treated with normal saline or Jisuikang by gavage on a daily basis for 14 days, and the changes in hindlimb motor function of the rats was assessed with Basso-Beattie-Bresnahan (BBB) scores and inclined-plate test. The injured spinal cord tissues were sampled from the SCI rat models for single-cell RNA sequencing, and bioinformatics analysis was performed to identify the target genes of Jisuikang, spinal cord injury and glycolysis. In the cell experiment, cultured astrocytes from neonatal SD rat cortex were treated with SOX2 alone or in combination with Jisuikang-medicated serum for 21 days, and the protein expressions of PKM2, p-PKM2 and YAP and colocalization of PKM2 and YAP in the cells were analyzed with Western blotting and immunofluorescence staining, respectively. Results The SCI rats with Jisuikang treatment showed significantly improved BBB scores and performance in inclined-plate test. At the injury site, high PKM2 expression was detected in various cell types. Bioinformatic analysis identified the HIPPO-YAP signaling pathway as the target pathway of Jisuikang. In cultured astrocytes, SOX2 combined with the mediated serum, as compared with SOX2 alone, significantly increased PKM2, p-PKM2 and YAP expressions and entry of phosphorylated PKM2 into the nucleus, and promoted PKM2 and YAP co-localization in the cells. Conclusion Jisuikang formula accelerates SCI repair in rats possibly by promoting aerobic glycolysis of the astrocytes via activating the PKM2/YAP axis to induce reprogramming of the astrocytes into neurons.
