BACKGROUND: Ischemia-reperfusion injury contributes significantly to the pathogenesis of chronic wounds such as pressure sores and diabetic foot ulcers. The authors' laboratory has previously developed a cyclical murine ischemia-reperfusion injury model. The authors here use this model to determine factors underlying tissue response to ischemia-reperfusion injury. METHODS: C57BL/6 mice were subjected to cycles of ischemia-reperfusion that varied in number (one to four cycles) and duration of ischemia (1 to 2 hours). For each ischemia-reperfusion condition, the following variables were analyzed: (1) digital photographs for area of necrosis; (2) hematoxylin and eosin staining and immunohistochemistry for inflammatory infiltrate; and (3) expression of inflammatory markers by quantitative polymerase chain reaction. In addition, human adipocytes and fibroblasts were cultured in vitro under conditions of hypoxia and reoxygenation, and expression of inflammatory markers was analyzed by quantitative polymerase chain reaction. RESULTS: Increases in both ischemia-reperfusion cycle number and ischemia duration correlated with increased areas of epithelial necrosis both grossly and histologically, and with an increase in cellularity and neutrophil density. This increased inflammatory infiltrate and a significant increase in the expression of proinflammatory markers (Hmox1, interleukin-6, interleukin-1, and monocyte chemoattractant protein-1) was observed in adipose tissue subjected to ischemia-reperfusion injury, but not in dermis. These results were mirrored in human adipose tissue. CONCLUSIONS: The authors further characterize a novel, reproducible murine model of ischemia-reperfusion injury. The results of their study indicate that adipose tissue is less tolerant of ischemia-reperfusion than dermal tissue. Rather than being an "innocent bystander," adipose tissue plays an active role in driving the inflammatory response to ischemia-reperfusion injury.
BACKGROUND:Ischemia-reperfusion injury contributes significantly to the pathogenesis of chronic wounds such as pressure sores and diabetic foot ulcers. The authors' laboratory has previously developed a cyclical murineischemia-reperfusion injury model. The authors here use this model to determine factors underlying tissue response to ischemia-reperfusion injury. METHODS: C57BL/6 mice were subjected to cycles of ischemia-reperfusion that varied in number (one to four cycles) and duration of ischemia (1 to 2 hours). For each ischemia-reperfusion condition, the following variables were analyzed: (1) digital photographs for area of necrosis; (2) hematoxylin and eosin staining and immunohistochemistry for inflammatory infiltrate; and (3) expression of inflammatory markers by quantitative polymerase chain reaction. In addition, human adipocytes and fibroblasts were cultured in vitro under conditions of hypoxia and reoxygenation, and expression of inflammatory markers was analyzed by quantitative polymerase chain reaction. RESULTS: Increases in both ischemia-reperfusion cycle number and ischemia duration correlated with increased areas of epithelial necrosis both grossly and histologically, and with an increase in cellularity and neutrophil density. This increased inflammatory infiltrate and a significant increase in the expression of proinflammatory markers (Hmox1, interleukin-6, interleukin-1, and monocyte chemoattractant protein-1) was observed in adipose tissue subjected to ischemia-reperfusion injury, but not in dermis. These results were mirrored in humanadipose tissue. CONCLUSIONS: The authors further characterize a novel, reproducible murine model of ischemia-reperfusion injury. The results of their study indicate that adipose tissue is less tolerant of ischemia-reperfusion than dermal tissue. Rather than being an "innocent bystander," adipose tissue plays an active role in driving the inflammatory response to ischemia-reperfusion injury.
Authors: Hua-Jun Wang; Shi-Xue Dai; Quan Lu; Lin-Chang Ye; Hua Li; Xi Song; Tao Hong; Wei-Hong Sha Journal: Nan Fang Yi Ke Da Xue Xue Bao Date: 2017-12-20