摘要：OBJECTIVE To investigate the effects of IMM-H004 on permanent focal cere-bral ischemia injury and associated cardiopulmonary complications, further elucidating the molecular mechanisms. METHODS The effects of IMM-H004 were investigated in wild-type (WT)and CKLF1^(-/-)rats. The effects of IMM-H004 on ischemic stroke injury and its cardiopulmonary complications were determined using 2, 3, 5-triphenyltetrazolium chloride (TTC) staining, behavior tests, magnetic resonance imaging (MRI) scans, enzyme-linked immunosorbent assay (ELISA), Nissl staining, and histo-pathological examination. Multiple molecular experiments including immunohistological staining, immunoflu-orescence staining, quantitative RT-PCR, Western blotting, and co-immunoprecipitation assays were used to elucidate the underlying mechanisms. RESULTS IMM-H004 treatment provided significant protection against ischemic stroke-induced brain injury and associated cardiopulmonary complications, through CKLF1-depedent-anti-inflammation pathway in rats. IMM-H004 down-regulated the amount of CKLF1 and disturbed the combination between CKLF1 and C-C chemokine receptor type 4, suppressing the inflammatory response and protecting the damaged organs in ischemic setting. CONCLUSION This preclinical study established efficacy of IMM-H004 as a potential therapeutic medicine for ischemic stroke and associated cardiopulmonary complications. The protective effects of IMM-H004 may due to its specific mechanism through CKLF1. These results support further efforts to develop IMM-H004 for human clinical trials in acute cere-bral ischemia, especially for patients who are not suitable for reperfusion therapy.

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