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白介素-20 受体通过重组白介素-19 激活增强实验性 GMH 大鼠幼仔模型血肿清除，通过白介素-20 受体 1/ERK/Nrf2 通路。

IL-20R Activation via rIL-19 Enhances Hematoma Resolution through the IL-20R1/ERK/Nrf2 Pathway in an Experimental GMH Rat Pup Model.

机构信息

Department of Pediatrics, Shenzhen People's Hospital, the Second Clinical Medical College of Jinan University, Shenzhen, Guangdong, China.

Department of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, California, USA.

出版信息

Oxid Med Cell Longev. 2021 Jan 19;2021:5913424. doi: 10.1155/2021/5913424. eCollection 2021.

DOI:10.1155/2021/5913424
PMID:33532035
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7837781/
Abstract

AIMS

Blood clots play the primary role in neurological deficits after germinal matrix hemorrhage (GMH). Previous studies have shown a beneficial effect in blood clot clearance after hemorrhagic stroke. The purpose of this study is to investigate interleukin-19's role in hematoma clearance after GMH and its underlying mechanism of IL-20R1/ERK/Nrf2 signaling pathway.

METHODS

A total of 240 Sprague-Dawley P7 rat pups were used. GMH was induced by intraparenchymal injection of bacterial collagenase. rIL-19 was administered intranasally 1 hour post-GMH. IL-20R1 CRISPR was administered intracerebroventricularly, or Nrf2 antagonist ML385 was administered intraperitoneally 48 hours and 1 hour before GMH induction, respectively. Neurobehavior, Western blot, immunohistochemistry, histology, and hemoglobin assay were used to evaluate treatment regiments in the short- and long-term.

RESULTS

Endogenous IL-19, IL-20R1, IL-20R2, and scavenger receptor CD163 were increased after GMH. rIL-19 treatment improved neurological deficits, reduced hematoma volume and hemoglobin content, reduced ventriculomegaly, and attenuated cortical thickness loss. Additionally, treatment increased ERK, Nrf2, and CD163 expression, whereas IL-20R1 CRISPR-knockdown plasmid and ML385 inhibited the effects of rIL-19 on CD163 expression.

CONCLUSION

rIL-19 treatment improved hematoma clearance and attenuated neurological deficits induced by GMH, which was mediated through the upregulation of the IL-20R1/ERK/Nrf2 pathways. rIL-19 treatment may provide a promising therapeutic strategy for the GMH patient population.

摘要

目的

在脑室内出血（GMH）后，血栓在神经功能缺损中起主要作用。先前的研究表明，在出血性中风后清除血栓有有益作用。本研究旨在探讨白细胞介素-19（IL-19）在 GMH 后血肿清除中的作用及其 IL-20R1/ERK/Nrf2 信号通路的潜在机制。

方法

共使用 240 只 P7 天龄 Sprague-Dawley 大鼠。GMH 通过脑实质内注射细菌胶原酶诱导。GMH 后 1 小时经鼻内给予 rIL-19。GMH 诱导前 48 小时和 1 小时分别经侧脑室给予 IL-20R1 CRISPR 和 Nrf2 拮抗剂 ML385。神经行为学、Western blot、免疫组织化学、组织学和血红蛋白测定用于评估短期和长期治疗方案。

结果

GMH 后，内源性 IL-19、IL-20R1、IL-20R2 和清道夫受体 CD163 增加。rIL-19 治疗改善了神经功能缺损，减少了血肿体积和血红蛋白含量，减轻了脑室扩大，并减轻了皮质厚度损失。此外，治疗增加了 ERK、Nrf2 和 CD163 的表达，而 IL-20R1 CRISPR 敲低质粒和 ML385 抑制了 rIL-19 对 CD163 表达的影响。

结论

rIL-19 治疗改善了 GMH 引起的血肿清除和神经功能缺损，这是通过上调 IL-20R1/ERK/Nrf2 途径介导的。rIL-19 治疗可能为 GMH 患者群体提供一种有前途的治疗策略。

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