Chinese Journal of Tissue Engineering Research ›› 2021, Vol. 25 ›› Issue (26): 4175-4179.doi: 10.12307/2021.117

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Lipoxanthin A4 plays a neuroprotective role against spinal cord ischemia-reperfusion injury in rats

Lu Tan1, Chang Yaohui2, Wei Na3   

  1. 1Department of Orthopedics, the First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, Henan Province, China; 2Department of Orthopedics, Xiuwu County People’s Hospital, Jiaozuo 454350, Henan Province, China; 3Department of Neurology, the Third Affiliated Hospital of Xinxiang Medical University, Xinxiang 453003, Henan Province, China
  • Received:2019-04-01 Revised:2019-05-06 Accepted:2020-08-11 Online:2021-09-18 Published:2021-05-10
  • Contact: Wei Na, Associate chief physician, Department of Neurology, the Third Affiliated Hospital of Xinxiang Medical University, Xinxiang 453003, Henan Province, China
  • About author:Lu Tan, MD, Associate chief physician, Master’s supervisor, Department of Orthopedics, the First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, Henan Province, China
  • Supported by:
    the Key Scientific Research Project of Henan Provincial Colleges and Universities, No. 19A320003 (to LT); Xinxiang Municipal Science and Technology Research Project, No. CXGG17031 (to WN); Youth Fund of the First Affiliated Hospital of Xinxiang Medical University, No. QN-2017-A002 (to LT)

Abstract:

BACKGROUND: Previous studies have indicated that lipoxin A4 has a neuroprotective effect against spinal cord injury in rats, but its mechanism of action in spinal cord ischemia-reperfusion injury is still unclear.

OBJECTIVE: To investigate the neuroprotective effect of lipoxin A4 in rats with spinal cord ischemia-reperfusion injury. 
METHODS: Forty-eight Sprague-Dawley rats were randomized into three groups (n=16 per group): Spinal cord ischemia-reperfusion injury models were built in control and experimental groups followed by intrathecal injection of normal saline and lipoxin A4 respectively, and no treatment was given in blank control group. Basso-Beattie-Bresnahan (BBB) score was used to evaluate motor nerve function in rats at 6, 12, 24, and 48 hours after modeling. At 24 hours after reperfusion, TUNEL assay was used to detect cell apoptosis in the rat spinal cord; ELISA was used to detect the levels of Bcl-2 and Bax in the rat spinal cord, and western blot assay was used to detect the levels of cleaved-caspase-3, p-IKKβ and p-NF-κB proteins in the rat spinal cord. This experiment was approved by the Ethics Committee of the First Affiliated Hospital of Xinxiang Medical University (approval No. 2018038).
RESULTS AND CONCLUSION: Compared with the blank control group, the BBB scores were lower in the control group at different observation time points 
(P < 0.05), while compared with the control group, the BBB score was higher in the experimental group at 12, 24, and 48 hours after modeling (P < 0.05). There were more apoptotic cells in the control group than the blank control group (P < 0.05), while the number of apoptotic cells in the experimental group was lower than that in the control group (P < 0.05). The levels of Bcl-2 and Bax in the spinal cord were significantly higher in the control group than the blank control group, while compared with the control group, the experimental group showed a higher Bcl-2 level and a lower Bax level (P < 0.05). Compared with the blank control group, the expressions of cleaved-caspase-3 and p-NF-κB proteins were strongly higher in the control group, while the protein expression of p-IKKβ was weaker in the control group. Compared with the control group, the expressions of cleaved-caspase-3 and p-NF-κB proteins were lower in the experimental group, while the protein expression of p-IKKβ was higher in the experimental group. These findings indicate that lipoxin A4, as a therapeutic agent for spinal cord ischemia-reperfusion injury, can inhibit cell apoptosis by activating the Caspase-3/IKKβ/NF-κB pathway in the cytoplasm.

Key words: tissue construction, spinal cord, lipoxin A4, spinal cord ischemia-reperfusion injury, apoptosis, signaling pathway

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