IMM-H004 Protects against Cerebral Ischemia Injury and Cardiopulmonary Complications via CKLF1 Mediated Inflammation Pathway in Adult and Aged Rats
IMM-H004 Protects against Cerebral Ischemia Injury and Cardiopulmonary Complications via CKLF1 Mediated Inflammation Pathway in Adult and Aged Rats
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IMM-H004 通过 CKLF1 介导的炎症途径保护成年和老年大鼠免受脑缺血损伤和心肺并发症
DOI：
10.3390/ijms20071661
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发表时间：
2019-04-01
影响因子：
5.6
通讯作者：
Chen, Naihong
中科院分区：
文献类型：
--
作者：
Ai, Qidi;Chen, Chen;Chen, Naihong
（1）背景：趋化因子样因子1（CKLF1）是一种趋化因子，有潜力成为中风治疗的靶点。化合物IMM - H004是从CKLF1/C - C趋化因子受体4型（CCR4）系统中筛选出的一种新型香豆素衍生物，据报道其可改善脑缺血/再灌注损伤。本研究旨在从CKLF1的角度，探究IMM - H004对成年及老年大鼠脑缺血损伤及其感染性心肺并发症的保护作用。
（2）方法：通过2,3,5 - 三苯基氯化四氮唑（TTC）染色、行为学测试、磁共振成像（MRI）扫描、酶联免疫吸附试验（ELISA）、尼氏染色、组织病理学检查以及心肺功能检测来确定IMM - H004的保护作用。采用免疫组织化学染色、免疫荧光染色、实时荧光定量聚合酶链反应（qPCR）和蛋白质免疫印迹法来阐明其潜在机制。
（3）结果：在成年及老年大鼠中，IMM - H004可减轻脑缺血所致的脑损伤及其心肺并发症，通过依赖CKLF1的抗炎途径抑制损伤和炎症反应。IMM - H004下调CKLF1的含量，抑制后续的炎症反应，进而保护受损器官免受缺血性损伤。
（4）结论：本研究表明，IMM - H004的保护机制依赖于CKLF1，CKLF1在脑缺血中会引发过度炎症反应。IMM - H004也可能成为治疗老年人群缺血性中风及其心肺并发症的治疗药物。
(1) Background: Chemokine-like factor 1 (CKLF1) is a chemokine with potential to be a target for stroke therapy. Compound IMM-H004 is a novel coumarin derivative screened from a CKLF1/C-C chemokine receptor type 4 (CCR4) system and has been reported to improve cerebral ischemia/reperfusion injury. This study aims to investigate the protective effects of IMM-H004 on cerebral ischemia injury and its infectious cardiopulmonary complications in adult and aged rats from the CKLF1 perspective. (2) Methods: The effects of IMM-H004 on the protection was determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining, behavior tests, magnetic resonance imaging (MRI) scans, enzyme-linked immunosorbent assay (ELISA), Nissl staining, histo-pathological examination, and cardiopulmonary function detection. Immunohistological staining, immunofluorescence staining, quantitative real-time PCR (qPCR), and western blotting were used to elucidate the underlying mechanisms. (3) Results: IMM-H004 protects against cerebral ischemia induced brain injury and its cardiopulmonary complications, inhibiting injury, and inflammation through CKLF1-dependent anti-inflammation pathway in adult and aged rats. IMM-H004 downregulates the amount of CKLF1, suppressing the followed inflammatory response, and further protects the damaged organs from ischemic injury. (4) Conclusions: The present study suggested that the protective mechanism of IMM-H004 is dependent on CKLF1, which will lead to excessive inflammatory response in cerebral ischemia. IMM-H004 could also be a therapeutic agent in therapy for ischemic stroke and cardiopulmonary complications in the aged population.