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Effect of recombinant human MG53 protein on tourniquet-induced ischemia-reperfusion injury in rat muscle.

ABSTRACT: INTRODUCTION:Skeletal muscle ischemia-reperfusion injury (I-R) is a complex injury process that includes damage to the sarcolemmal membrane, contributing to necrosis and apoptosis. MG53, a muscle-specific TRIM family protein, has been shown to be essential for regulating membrane repair and has been shown to be protective against cardiac I-R and various forms of skeletal muscle injury. The purpose of this study was to determine if recombinant human MG53 (rhMG53) administration offered protection against I-R. METHODS:rhMG53 was administered to rats immediately before tourniquet-induced ischemia and again immediately before reperfusion. Two days later muscle damage was assessed histologically. RESULTS:rhMG53 offered no protective effect, as evidenced primarily by similar Evans blue dye inclusion in the muscles of rats administered rhMG53 or saline. CONCLUSIONS:Administration of rhMG53 does not offer protection against I-R in rat skeletal muscle. Additional studies are required to determine if the lack of a response is species-specific.

SUBMITTER: Corona BT

PROVIDER: S-EPMC4028410 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Effect of recombinant human MG53 protein on tourniquet-induced ischemia-reperfusion injury in rat muscle.

Corona Benjamin T BT Garg Koyal K Roe Janet L JL Zhu Hua H Park Ki Ho KH Ma Jianjie J Walters Thomas J TJ

Muscle & nerve 20140601 6

<h4>Introduction</h4>Skeletal muscle ischemia-reperfusion injury (I-R) is a complex injury process that includes damage to the sarcolemmal membrane, contributing to necrosis and apoptosis. MG53, a muscle-specific TRIM family protein, has been shown to be essential for regulating membrane repair and has been shown to be protective against cardiac I-R and various forms of skeletal muscle injury. The purpose of this study was to determine if recombinant human MG53 (rhMG53) administration offered pr ...[more]

PMID: 24395153

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Project description:Acute ischemia reperfusion injury in skeletal muscle remains an important issue in several fields of regenerative medicine. Thus, a valid model is essential to gain deeper insights into pathophysiological relations and evaluate possible treatment options. While the vascular anatomy of mice regularly prevents sufficient vessel occlusion by invasive methods, there is a multitude of existing models to induce ischemia reperfusion injury without surgical procedures. Since there is no consensus on which model to prefer, this study aims to develop and evaluate a novel, optimized low-pressure tourniquet model. C57BL/6 mice underwent an ischemic procedure by either tourniquet or invasive artery clamping. A sham group served as control. With exception of the sham group, mice underwent 2 hours of ischemia followed by 4 hours of reperfusion. Groups were compared using microcirculatory and spectroscopic measurements, distinctions in tissue edema, histological and immunohistochemical analyses. Both procedures led to a significant decrease in tissue blood flow (- 97% vs. - 86%) and oxygenation (- 87% vs. - 75%) with a superiority of the low-pressure tourniquet. Tissue edema in the tourniquet cohort was significantly increased (+ 59%), while the increase in the clamping cohort was non-significant (+ 7%). Haematoxylin Eosin staining showed significantly more impaired muscle fibers in the tourniquet group (+ 77 p.p. vs. + 11 p.p.) and increased neutrophil infiltration/ROI (+ 51 vs. + 8). Immunofluorescence demonstrated an equal increase of p38 in both groups (7-fold vs. 8-fold), while the increase in apoptotic markers (Caspase-3, 3-Nitrotyrosine, 4-Hydroxynonenal) was significantly higher in the tourniquet group. The low-pressure tourniquet has been proven to produce reproducible and thus reliable ischemia reperfusion injury. In addition, significantly less force was needed than previously stated. It is therefore an important instrument for studying the pathophysiology of ischemia reperfusion injury and for the development of prophylactic as well as therapeutic interventions.

Dataset Information

Effect of recombinant human MG53 protein on tourniquet-induced ischemia-reperfusion injury in rat muscle.

Publications

Effect of recombinant human MG53 protein on tourniquet-induced ischemia-reperfusion injury in rat muscle.

Similar Datasets

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