Arginase-2 protects myocardial ischemia-reperfusion injury via NF-κB/TNF-α pathway
Authors: P-H Du
X-W Huang
M-D Pan
L-X Wang
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Arginase-2; Ischemia-reperfusion injury; NF-κB; TNF-α; Rats
Affiliations: Department of Emergency, the First Affiliated Hospital of Xiamen University, Xiamen, China. .

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 &lt; 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 &lt; 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. 

Retracted: No

PubPeer comments:
 Figure 7C. * Red boxes: the middle GAPDH panel appears to look similar to the right GAPDH panel, if one of the two is rotated 180 degrees. Lower panels presumed to be GAPDH panels. ![file] , 
  Figure 4 ABE treatment enhances femoral head neovascularization. (A) Representative images of micro-CT reconstructed 3-D microangiography of proximal femur from control, model, ABE 10 g kg, ABE 15 g kg, and ABE 22.5 g kg groups . Two areas of unexpectedly similar vasculature in the Control and ABE 10g kg femurs: ![] More areas of similar vasculature between the ABE 10 and ABE 15 g kg femurs: ![] Perhaps the greatest coincidence, though, is the appearance of indistinguishable vasculature reconstructions in Fig 2 of [Jiang et al (2014)] , where they characterised the effect of Huogu u2160: ![] And in Fig 2 of [Jiang et al (2014b)] where they characterised the effect of Pravastatin. ![] , 
  Figure 2 ABE treatment enhances osteogenesis and reverses bone marrow adipogenesis. (A) Histological features of normal bone from a normal rat, and osteonecrotic bone from rats with steroid-induced ONFH with or without ABE treatment ![] Overlap between the ABE 15g kg and ABE 22.5g kg panels (though also with some unexpected differences in the area of overlap). ![] A close-up of the overlapping area to emphasize the differences. ![file] ,