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雷公藤内酯醇通过调控 Wnt/β-连环蛋白信号通路减轻大鼠脑缺血再灌注损伤。

Triptolide mediates Wnt/β-catenin signalling pathway to reduce cerebral ischemia-reperfusion injury in rats.

机构信息

Department of Neurosurgery, Qingdao Chengyang People's Hospital, Qingdao, China.

Department of Neurosurgery, Qingdao Municipal Hospital, Qingdao, China.

出版信息

Folia Neuropathol. 2020;58(4):324-333. doi: 10.5114/fn.2020.102435.

DOI:10.5114/fn.2020.102435
PMID:33480237
Abstract

INTRODUCTION

Triptolide, extracted from Chinese medicinal materials Tripterygium wilfordii Hook F (TwHF), has immunosuppressive, anti-inflammatory and anti-tumour effects. The purpose of this study was to examine whether triptolide has the neuroprotective effect on cerebral ischemia-reperfusion (I/R) injury and to explore its possible mechanism.

MATERIAL AND METHODS

The rat model of focal cerebral I/R was established by the suture-occluded method. The SD rats were randomly divided into five groups: sham operation group (Sham group), ischemia-reperfusion model group (I/R group), low concentration of triptolide group (12.5 mg/kg, TL-L group), medium concentration of triptolide group (25 mg/kg, TL-M group) and high concentration of triptolide group (50 mg/kg, TL-H group). The neurological function of the rats was scored, the degree of brain oedema was detected by the dry-wet method, and the cerebral infarction area was determined by TTC staining. Nissl staining was used to detect neuronal damage. The contents of reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) were also detected. Meanwhile, the expression level of proteins related to Wnt/-catenin signalling pathway was measured by Western blot.

RESULTS

Compared with the I/R group, cerebral oedema, infarct volume, neurological impairment, the contents of MDA and ROS were reduced, while the SOD level was increased in the TL-L, TL-M, and TL-H groups. The results of Nissl staining showed that triptolide could reduce the nerve cell injury caused by cerebral I/R. In addition, the results of Western blot confirmed that the expression of Wnt1, -catenin, c-Myc, and Cyclin-D1 were down-regulated after triptolide intervention, that is, inhibited the activation of Wnt/-catenin signalling pathway.

CONCLUSIONS

Triptolide mediates Wnt/-catenin signalling pathway to alleviate cerebral I/R injury in rats. This study provides ideas and experimental basis for the treatment of ischemic stroke patients.

摘要

简介

雷公藤红素是从中药雷公藤(TwHF)中提取的,具有免疫抑制、抗炎和抗肿瘤作用。本研究旨在探讨雷公藤红素是否对脑缺血再灌注(I/R)损伤具有神经保护作用,并探讨其可能的机制。

材料与方法

采用线栓法建立大鼠局灶性脑 I/R 模型。将 SD 大鼠随机分为五组:假手术组(Sham 组)、缺血再灌注模型组(I/R 组)、低浓度雷公藤红素组(12.5mg/kg,TL-L 组)、中浓度雷公藤红素组(25mg/kg,TL-M 组)和高浓度雷公藤红素组(50mg/kg,TL-H 组)。对大鼠的神经功能进行评分,采用干湿法检测脑水肿程度,采用 TTC 染色法测定脑梗死面积。Nissl 染色法检测神经元损伤情况。同时,采用 Western blot 法检测与 Wnt/β-连环蛋白信号通路相关蛋白的表达水平。

结果

与 I/R 组相比,TL-L、TL-M 和 TL-H 组脑水肿、梗死体积、神经功能损伤减轻,MDA 和 ROS 含量降低,SOD 水平升高。Nissl 染色结果显示,雷公藤红素可减轻脑 I/R 引起的神经细胞损伤。此外,Western blot 结果证实,雷公藤红素干预后 Wnt1、β-连环蛋白、c-Myc 和 Cyclin-D1 的表达下调,即抑制了 Wnt/β-连环蛋白信号通路的激活。

结论

雷公藤红素通过介导 Wnt/β-连环蛋白信号通路减轻大鼠脑 I/R 损伤。本研究为缺血性脑卒中患者的治疗提供了思路和实验依据。

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