缺血后调适对骨骼肌缺血再灌注损伤的保护及其机制的初步探讨

BACKGROUND: Reperfusion injury salvage kinase (RISK) pathway plays an important role in protective mechanism against ischemia reperfusion injury (IRI) induced by both ischemic pre- and post-conditioning. Many researches have been carried out on RISK pathway mechanism underlying ischemic post-conditioning conferring cardioprotection against IRI; however, there is less research about its effect on IRI in the skeletal muscle. OBJECTIVE: To investigate the protective effect of an optimized protocol of ischemic post-conditioning on   IRI in rat skeletal muscle and its underlying mechanism. METHODS: Eighteen male Sprague-Dawley rats were equivalently randomized into IRI, ischemic post-conditioning and control groups. Rats were given occlusion or disocclusion of the right femoral artery of the right lower limb. Subsequently, the IRI group rats were subjected to 24 hours of reperfusion; the ischemic post-conditioning group immediately given 4 cycles of 30 seconds reperfusion/30 seconds ischemia, followed by 24 hours of reperfusion; the control group given no intervention. RESULTS AND CONCLUSION: Hematoxylin-eosin staining showed that in the ischemic post-conditioning group, the morphology of muscle fibers changed little, with fewer inflammatory lesions and milder edema compared with the IRI group. The infarct size with TTC staining in the ischemic post-conditioning group was smaller than that in the IRI group. Western blot analysis revealed that the expressions of phospho-Akt and phosphorylated endothelial nitric oxide synthase-S1177 were significantly increased, but the expression of phosphorylated type endothelial nitric oxide synthase-Thr495 was much decreased in the ischemic post-conditioning group compared with the IRI group. The measurement of mitochondrial permeability transition pore opening with Ca2+ induction showed that the absorbance values in the ischemic post-conditioning group were significantly lower than those in the IRI group (P < 0.05). These results indicate that ischemia-reperfusion injury can be improved by applying an optimal protocol of ischemic post-conditioning in rat skeletal muscle. The underlying mechanism may be associated with the activation of RISK signaling pathway to inhibit opening of mitochondrial permeability transition pore, thereby contributing to the enhanced tolerance to IRI in rat skeletal muscle. 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Ischemic post-conditioning protects against ischemia-reperfusion injury in the skeletal muscle: a preliminary research on its mechanism