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.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Arginase/pharmacology , Myocardial Infarction/prevention & control , Myocardial Reperfusion Injury/prevention & control , Myocytes, Cardiac/drug effects , NF-kappa B/metabolism , Tumor Necrosis Factor-alpha/metabolism , Animals , Apoptosis/drug effects , Cell Proliferation/drug effects , Creatine Kinase, MB Form/blood , Cytoprotection , Disease Models, Animal , Heart Rate/drug effects , L-Lactate Dehydrogenase/blood , Male , Myocardial Infarction/metabolism , Myocardial Infarction/pathology , Myocardial Infarction/physiopathology , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/pathology , Myocardial Reperfusion Injury/physiopathology , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Rats, Sprague-Dawley , Signal TransductionABSTRACT
BACKGROUND: Prognostic blood biomarkers in the setting of acute ischemic stroke have become increasingly relevant for risk stratification, monitoring disease and response to therapies, developing targets for neuroprotective treatment and as surrogate end points for treatment trials. AIM: We aim to find the feature genes which can accurately detect acute ischemic stroke and perform function analysis of these crucial genes in peripheral blood mononuclear cells. MATERIALS AND METHODS: The gene expression profile GSE22255 was downloaded from Gene Expression Omnibus (GEO) database which includes 20 ischemic stroke patients and 20 controls. The differentially expressed genes between patients and controls samples were identified with packages in R language. The selected differentially expressed genes were further analyzed using bioinformatics methods. Software STRING (Search Tool for the Retrieval of Interacting Genes) was used to establish co-expression network. GOTM (General Ocean Turbulence Model) software was used to obtain differentially expressed gene enriched modules. The functions of genes in modules were analyzed by using software GeneCodis. RESULTS: A total of 37 genes were identified as differentially expressed genes by comparing peripheral blood mononuclear cells gene expression of ischemic stroke patients and 20 controls. A co-expression network was constructed within 30 differentially expressed genes, among which gene interleukin-8 (IL-8) and tumor necrosis factor (TNF) showed the highest node degree. Genes in the module containing IL-8 and TNF were significantly enriched in 6 biological functions, and the most significant function was respond to stimulation. CONCLUSIONS: Our results highlight that genes IL-8 and TNF have close relationship with acute ischemic stroke, and the expression patterns of these genes may be valid targets for new medications able to modify the ischemic stroke process.
