Calpain inhibition ameliorates scald burn-induced acute lung injury in rats
| العنوان: | Calpain inhibition ameliorates scald burn-induced acute lung injury in rats |
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| المؤلفون: | Ke Tao, Xi-Xiang Lin, Li-Feng Wang, Xiao-Ming Gu, Hong-Ting Lu, Yan-Xia Wang, Xiao-Zhi Bai, Jing-Jun Zhou, Peng-Ran Du |
| المصدر: | Burns & Trauma, Vol 6, Iss 1, Pp 1-9 (2018) Burns & Trauma |
| بيانات النشر: | Oxford University Press (OUP), 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Burn injury, medicine.medical_specialty, Biomedical Engineering, lcsh:Medicine, Burn, Inflammation, Dermatology, Lung injury, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, Western blot, Internal medicine, Acute lung injury, Scalding, medicine, Immunology and Allergy, Lung, Membrane skeleton proteins, biology, medicine.diagnostic_test, Calpain, business.industry, lcsh:R, 030208 emergency & critical care medicine, medicine.disease, Scald, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Emergency Medicine, biology.protein, Surgery, medicine.symptom, business, Total body surface area, Research Article |
| الوصف: | Background The molecular pattern of severe burn-induced acute lung injury, characterized by cell structure damage and leukocyte infiltration, remains unknown. This study aimed to determine whether calpain, a protease involved in both processes, mediates severe burn-induced acute lung injury. Methods Rats received full-thickness scald burns covering 30% of the total body surface area, followed by instant fluid resuscitation. MDL28170 (Tocris Bioscience), an inhibitor of calpain, was given intravenously 1 h before or after the scald burn. The histological score, wet/dry weight ratio, and caspase-3 activity were examined to evaluate the degree of lung damage. Calpain activity and its source were detected by an assay kit and immunofluorescence staining. The proteolysis of membrane skeleton proteins α-fodrin and ankyrin-B, which are substrates of calpain, was measured by Western blot. Results Time-course studies showed that tissue damage reached a peak between 1 and 6 h post-scald burn and gradually diminished at 24 h. More importantly, calpain activity reached peak levels at 1 h and was maintained until 24 h, paralleled by lung damage to some extent. Western blot showed that the levels of the proteolyzed forms of α-fodrin and ankyrin-B correlated well with the degree of damage. MDL28170 at a dose of 3 mg/kg b. w. given 1 h before burn injury not only antagonized the increase in calpain activity but also ameliorated scald burn-induced lung injury, including the degradation of α-fodrin and ankyrin-B. Immunofluorescence images revealed calpain 1 and CD45 double-positive cells in the lung tissue of rats exposed to scald burn injury, suggesting that leukocytes were a dominant source of calpain. Furthermore, this change was blocked by MDL28170. Finally, MDL28170 given at 1 h post-scald burn injury significantly ameliorated the wet/dry weight ratio compared with burn injury alone. Conclusions Calpain, a product of infiltrating leukocytes, is a mediator of scald burn-induced acute lung injury that involves enhancement of inflammation and proteolysis of membrane skeleton proteins. Its late effects warrant further study. |
| تدمد: | 2321-3876 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e76747946590828cdef1c442c0d55369 https://doi.org/10.1186/s41038-018-0130-3 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....e76747946590828cdef1c442c0d55369 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 23213876 |
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