PF4 通过 NF-κB 信号通路诱导脑出血大鼠的炎症反应。

PF4 induces inflammatory response through NF-kB signal pathway in rats with intracerebral haemorrhage.

机构信息

Hebei Normal University Biology Postdoctoral Research Station, College of Life Science, Hebei Normal University, China.

Hebei University of Chinese Medicine, China.

出版信息

Folia Neuropathol. 2023;61(4):379-386. doi: 10.5114/fn.2023.130449.

DOI:10.5114/fn.2023.130449

PMID:38174673

Abstract

Intracerebral haemorrhage (ICH) is a lethal cerebrovascular disorder with a high mortality and morbidity. Although it is a major public health problem, there is no effective treatment for ICH. After ICH, the primary and secondary mechanisms are mentioned when discussing brain injury. The transcription factor, nuclear factor-kappa B (NF-kB), is an important regulator of inflammatory responses. The role of platelet factor 4 (PF4) in ICH is unclear. To study the effect of PF4 on inflammatory response of rats in ICH, a rat model of striatum ICH was established by injecting autologous blood from the autogenous femoral artery into the right striatum of rats. Forty-eight hours after ICH, the expression of PF4, NF-kB (P-P65) and inflammatory changes in rats were determined with WB and ELISA. Heme was used to induce PC12 cell damage, simulate the ICH model in vitro, and detect PF4, P-P65 and striatal inflammatory changes. Short hairpin RNA (shRNA-PF4) was used to knock-down the expression of PF4 in PC12 cells to detect changes in inflammatory factors. The results showed that 48 hours after surgery, the behavioural score of cerebral haemorrhage was the lowest. The expression of PF4 and P-P65 in the striatum of the ICH group was significantly higher compared with the sham surgery group. The expression of interleukin (IL)-6 and IL-1b in the ICH group was also greatly improved. After inhibiting NF-kB expression, PF4 expression was decreased. In short, ICH enhances the expression of PF4, which induces an inflammatory response in rats with cerebral haemorrhage through the NF-kB signalling pathway. Reducing the expression of PF4 can attenuate the inflammatory response.

摘要

脑出血（ICH）是一种致命的脑血管疾病，具有高死亡率和高发病率。尽管它是一个主要的公共卫生问题，但目前尚无有效的治疗方法。ICH 发生后，在讨论脑损伤时会提到原发性和继发性机制。转录因子核因子-κB（NF-κB）是炎症反应的重要调节剂。血小板因子 4（PF4）在 ICH 中的作用尚不清楚。为了研究 PF4 对 ICH 大鼠炎症反应的影响，通过从自体股动脉向大鼠右侧纹状体注射自体血，建立了大鼠纹状体 ICH 模型。ICH 后 48 小时，通过 WB 和 ELISA 测定大鼠 PF4、NF-κB（P-P65）和炎症变化的表达。用血红素诱导 PC12 细胞损伤，模拟体外 ICH 模型，并检测 PF4、P-P65 和纹状体炎症变化。短发夹 RNA（shRNA-PF4）用于敲低 PC12 细胞中 PF4 的表达，以检测炎症因子的变化。结果表明，手术后 48 小时，脑出血的行为评分最低。ICH 组纹状体中 PF4 和 P-P65 的表达明显高于假手术组。ICH 组白细胞介素（IL）-6 和 IL-1b 的表达也大大提高。抑制 NF-κB 表达后，PF4 的表达减少。简而言之，ICH 增强了 PF4 的表达，通过 NF-κB 信号通路诱导脑出血大鼠的炎症反应。降低 PF4 的表达可以减轻炎症反应。