紫草素通过调控HMGB1/TLR4/NF-κB信号通路对大鼠脊髓损伤的影响

Effect of Shikonin on Spinal Cord Injury in Rats Via Regulation of HMGB1/TLR4/NF-kB Signaling Pathway.

作者信息

Bi Yihui, Zhu Yapeng, Zhang Mingkai, Zhang Keke, Hua Xingyi, Fang Zheng, Zhou Jian, Dai Wenjie, Cui Yixing, Li Jun, You Tao

机构信息

Department of orthopaedic, The First Affliated hospital, Anhui Medical University, HeFei, China.

Department of orthopaedic, Tongling pepole's hospital, TongLing, China.

出版信息

Cell Physiol Biochem. 2017;43(2):481-491. doi: 10.1159/000480474. Epub 2017 Sep 20.

DOI:10.1159/000480474

PMID:28934735

Abstract

BACKGROUND/AIMS: Shikonin, a compound extracted from Zicao, has been demonstrated to hold anti-bacterial, anti-inflammatory, and anti-tumor activities in various diseases and it has been shown to protect human organs from injuries. However, the effect of shikonin on the recovery of spinal cord injury (SCI) remains unknown. This study was designed to estimate the potential therapeutic effect and underlying mechanism of shikonin on SCI in vivo.

METHODS

In the study, we used HE staining, ELISA assay, transfection assay, TUNEL assay, real time PCR and Western blot to detect the effects of shikonin on spinal cord injury in rats.

RESULTS

we showed that shikonin could promote the recovery of motor function and tissue repair after SCI treatment in rats SCI model. Moreover, we demonstrated that shikonin inhibited the spinal cord edema in SCI model of rats. According to further investigation, shikonin induced the reduction of inflammatory response through decreasing the expression levels of HMGB1, TLR4 and NF-κB after SCI injury. In addition, we also found that shikonin could suppress the apoptosis and expression of caspase-3 protein in SCI model of rats.

CONCLUSION

Our results demonstrated that shikonin induced the recovery of tissue repair and motor function via inactivation of HMGB1/TLR4/NF-κB signaling pathway in SCI model of rats. Meanwhile, shikonin regulated the inflammation response in SCI by suppressing the HMGB1/TLR4/NF-κB signaling pathway. The described mechanism sheds novel light on molecular signaling pathway in spinal cord injury and secondary injury including inflammatory response.

摘要

背景/目的：紫草素是从紫草中提取的一种化合物，已被证明在多种疾病中具有抗菌、抗炎和抗肿瘤活性，并且已显示出能保护人体器官免受损伤。然而，紫草素对脊髓损伤（SCI）恢复的影响尚不清楚。本研究旨在评估紫草素在体内对SCI的潜在治疗作用及潜在机制。

方法

在本研究中，我们使用苏木精-伊红（HE）染色、酶联免疫吸附测定（ELISA）、转染测定、末端脱氧核苷酸转移酶介导的缺口末端标记（TUNEL）测定、实时聚合酶链反应（PCR）和蛋白质免疫印迹法（Western blot）来检测紫草素对大鼠脊髓损伤的影响。

结果

我们发现紫草素能够促进大鼠SCI模型在接受SCI治疗后运动功能的恢复和组织修复。此外，我们证明紫草素可抑制大鼠SCI模型中的脊髓水肿。进一步研究表明，紫草素通过降低SCI损伤后高迁移率族蛋白B1（HMGB1）、Toll样受体4（TLR4）和核因子κB（NF-κB）的表达水平来诱导炎症反应的减轻。此外，我们还发现紫草素可以抑制大鼠SCI模型中的细胞凋亡和半胱天冬酶-3（caspase-3）蛋白的表达。