Baicalein Attenuates Pyroptosis and Endoplasmic Reticulum Stress Following Spinal Cord Ischemia-Reperfusion Injury via Autophagy Enhancement

Chenyu Wu; Hui Xu; Jiafeng Li; Xinli Hu; Xingyu Wang; Yijia Huang; Yao Li; Sunren Sheng; Yongli Wang; Huazi Xu; Wenfei Ni; Kailiang Zhou

doi:10.3389/fphar.2020.01076

Baicalein Attenuates Pyroptosis and Endoplasmic Reticulum Stress Following Spinal Cord Ischemia-Reperfusion Injury via Autophagy Enhancement

Front Pharmacol. 2020 Jul 30:11:1076. doi: 10.3389/fphar.2020.01076. eCollection 2020.

Authors

Chenyu Wu^{1

2}, Hui Xu^{1

2}, Jiafeng Li^{1

2}, Xinli Hu^{1

2}, Xingyu Wang^{1

2}, Yijia Huang^{1

2}, Yao Li^{1

2}, Sunren Sheng^{1

2}, Yongli Wang³, Huazi Xu^{1

2}, Wenfei Ni^{1

2}, Kailiang Zhou^{1

2}

Affiliations

¹ Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
² Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China.
³ Department of Orthopaedics, Huzhou Central Hospital, Huzhou, China.

Abstract

Background: Spinal cord ischemia-reperfusion injury (SCIRI) is the main complication after the repair of a complex thoracoabdominal aortic aneurysm. Many clinical treatments are not ideal due to the complex pathophysiological process of this injury. Baicalein (BA), a component derived from the roots of the herb Scutellaria baicalensis, may contribute to the successful treatment of ischemia/reperfusion injury.

Purpose: In the present study, the effects of BA on spinal cord ischemia-reperfusion injury and the underlying mechanisms were assessed.

Materials and methods: Spinal cord ischemia was induced in C57BL/6 mice by blocking the aortic arch. Fifty-five mice were then randomly divided into four groups: Sham, SCIR+Vehicle, SCIR+BA, and SCIR+BA +3MA groups. At 0 and 24 h pre-SCIRI and at 24 h and 7 days post-SCIRI, evaluations with the Basso mouse scale (BMS) were performed. On postoperative 24 h, the spinal cord was harvested to assess pyroptosis, endoplasmic reticulum stress mediated apoptosis and autophagy.

Results: BA enhanced the functional recovery of spinal cord ischemia-reperfusion injury. In addition, BA attenuated pyroptosis, alleviated endoplasmic reticulum stress-mediated apoptosis, and activated autophagy. However, the effects of BA on the functional recovery of SCIRI, pyroptosis and endoplasmic reticulum stress-mediated apoptosis were reversed by the inhibition of autophagy.

Conclusions: In general, our findings revealed that BA enhances the functional recovery of spinal cord ischemia-reperfusion injury by dampening pyroptosis and alleviating endoplasmic reticulum stress-mediated apoptosis, which are mediated by the activation of autophagy.

Keywords: autophagy; baicalein; endoplasmic reticulum stress; pyroptosis; spinal cord ischemia-reperfusion injury.