早期和晚期分别给予吡咯烷二硫代氨基甲酸盐和十四烷酰佛波醇乙酸酯通过 NF-κB 通路减少大鼠脑出血后的继发性脑损伤。

Separate administration of ammonium pyrrolidinedithiocarbamate and phorbol myristate acetate at early and late stages decreases secondary brain injury following intracerebral haemorrhage in rats via the NF-κB pathway.

机构信息

Department of Neurosurgical Intensive Care Unit and Emergency Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute of Shandong University, Jinan, Shandong Province, P. R. China.

Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute of Shandong University, Jinan, Shandong Province, P. R. China.

出版信息

Folia Neuropathol. 2020;58(2):166-175. doi: 10.5114/fn.2020.96801.

DOI:10.5114/fn.2020.96801

PMID:32729295

Abstract

INTRODUCTION

Nuclear factor-kB (NF-kB) is a critical regulator of inflammatory responses following intracerebral haemorrhage (ICH). According to our previous study, inhibiting the p65 subunit at an early stage after ICH can reduce cell death, while inhibiting c-Rel at a late stage can lead to the opposite result. The aim of this study is to clarify whether patient prognosis can be improved by inhibiting p65 at the early stage and promoting c-Rel at the late stage.

MATERIAL AND METHODS

Rats were divided into a sham group, ICH group, early NF-kB-inhibiting group using ammonium pyrrolidinedithiocarbamate (PDTC; group A, p65 subunit was dominant and inhibited at the early stage), late NF-kB-activating group using phorbol myristate acetate (PMA; group B, c-Rel was dominant and promoted at the late stage), and early NF-kB-inhibiting and late-activating group (group C, p65 subunit was inhibited at the early stage and c-Rel was promoted at the late stage). At preset time points after ICH, perihematomal tissue was obtained for detection of NF-kB activation, cell death, and expression of caspase-3, Bcl-2, and NF-kB subunits, to evaluate of the effect of PDTC and PMA.

RESULTS

At four days after ICH, p65 expression (p < 0.01) and the number of TUNEL-positive cells (p < 0.01) in group A were significantly lower than in the ICH group. At 10 days after ICH, c-Rel expression in groups B and C was significantly higher than in other groups (p < 0.01 for all). TUNEL-positive cell numbers in groups A and B were significantly lower than in the ICH group, though more numerous than in group C (p < 0.01 for all).

CONCLUSIONS

Administration of both PDTC at the early stage and PMA at the late stage reduced perihematomal cell death after ICH, and using the two reagents together had a stronger anti-apoptotic effect than separate usage.

摘要

简介

核因子-κB（NF-κB）是脑出血（ICH）后炎症反应的关键调节因子。根据我们之前的研究，ICH 后早期抑制 p65 亚基可以减少细胞死亡，而晚期抑制 c-Rel 则会产生相反的结果。本研究旨在阐明通过早期抑制 p65 和晚期促进 c-Rel 是否可以改善患者预后。

材料和方法

将大鼠分为假手术组、ICH 组、早期 NF-κB 抑制组（使用吡咯烷二硫代氨基甲酸盐（PDTC；A 组，p65 亚基为主，早期抑制））、晚期 NF-κB 激活组（使用十四烷酰佛波醇乙酸酯（PMA；B 组，c-Rel 为主，晚期促进））和早期 NF-κB 抑制和晚期激活组（C 组，早期抑制 p65 亚基，晚期促进 c-Rel）。ICH 后预设时间点，获取血肿周围组织，检测 NF-κB 激活、细胞死亡以及 caspase-3、Bcl-2 和 NF-κB 亚基的表达，以评估 PDTC 和 PMA 的作用。