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黄芩苷减轻脊髓缺血再灌注损伤后的细胞焦亡和内质网应激 增强自噬。

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

作者信息

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

机构信息

Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China.

出版信息

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

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 , 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.

摘要

背景

脊髓缺血再灌注损伤(SCIRI)是复杂胸腹主动脉瘤修复术后的主要并发症。由于这种损伤复杂的病理生理过程,许多临床治疗并不理想。黄芩苷(BA)是一种从黄芩根中提取的成分,可能有助于成功治疗缺血/再灌注损伤。

目的

在本研究中,评估了BA对脊髓缺血再灌注损伤的影响及其潜在机制。

材料与方法

通过阻断主动脉弓在C57BL/6小鼠中诱导脊髓缺血。然后将55只小鼠随机分为四组:假手术组、SCIR+溶媒组、SCIR+BA组和SCIR+BA+3MA组。在SCIRI前0小时和24小时以及SCIRI后24小时和7天,用Basso小鼠评分(BMS)进行评估。术后24小时,取脊髓评估焦亡、内质网应激介导的凋亡和自噬。

结果

BA增强了脊髓缺血再灌注损伤的功能恢复。此外,BA减轻了焦亡,缓解了内质网应激介导的凋亡,并激活了自噬。然而,自噬的抑制逆转了BA对SCIRI功能恢复、焦亡和内质网应激介导的凋亡的影响。

结论

总体而言,我们的研究结果表明,BA通过抑制焦亡和缓解内质网应激介导的凋亡来增强脊髓缺血再灌注损伤的功能恢复,而这是由自噬的激活介导的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83b6/7438740/cf5b617a61af/fphar-11-01076-g001.jpg

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