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  • Title: Arginase-2 protects myocardial ischemia-reperfusion injury via NF-κB/TNF-α pathway.
    Author: Huang XW, Pan MD, Du PH, Wang LX.
    Journal: Eur Rev Med Pharmacol Sci; 2018 Oct; 22(19):6529-6537. PubMed ID: 30338823.
    Abstract:
    OBJECTIVE: Arginase-2 exerts an anti-inflammatory potential. However, whether nuclear factor-κB (NF-κB)/TNF-α (tumor necrosis factor-α) pathway is involved in the anti-inflammation effect of arginase-2 has not been fully elucidated. Our study aims to explore the regulatory role of arginase-2 on ischemia-reperfusion injury (IRI) in rats and its underlying mechanism. MATERIALS AND METHODS: 24 male Sprague Dawley (SD) rats were randomly assigned into sham group, IRI group and arginase-2 group, with 8 rats in each group. Electrocardiogram was performed in each rat before and after animal procedures. Serum samples and heart samples of each rat were collected 10 days after animal procedures. Serum levels of CK-MB (creatine kinase-MB) and LDH (lactate dehydrogenase) in each rat were detected using the relative commercial kits. Pathological lesions in rat myocardium were observed by hematoxylin and eosin (HE) staining. Cardiomyocyte apoptosis in rat heart was accessed by TUNEL (Terminal Deoxynucleotidyl Transferase dUTP Nick-end Labeling) staining. Expression levels of NF-κB, TNF-α, VCAM-1, ICAM-1 and MCP-1 in rat myocardium were detected by Western blot and immunohistochemistry. RESULTS: Electrocardiogram showed slower heart rate, lower voltage of QRS wave and longer Q-T interval in rats of IRI group than those of sham group (p < 0.05). A few rats in IRI group even presented arrhythmia. On the contrary, rats in arginase-2 group presented higher heart rate and voltage of QRS wave, as well as shorter Q-T interval compared with those of IRI group (p < 0.05). Rats in arginase-2 group presented lower plasma levels of CK-MB and LDH than those of IRI group. Pathological lesions in rat myocardium and cardiomyocyte apoptosis were alleviated in arginase-2 group in comparison with those of IRI group. Western blot and immunohistochemistry indicated that arginase-2 pretreatment remarkably downregulated expressions of NF-κB, TNF-α, VCAM-1, ICAM-1 and MCP-1 in rat myocardium. CONCLUSIONS: Arginase-2 protects myocardial ischemia-reperfusion injury in rats through inhibiting the inflammatory response via suppression of NF-κB/TNF-α pathway.
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