Lin Hai-Peng, Zheng Yan-Qing, Zhou Zhi-Ping, Wang Gao-Xiong, Guo Ping-Fan
Department of General Surgery, the Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.
Department of E.N.T, Quanzhou Women's and Children's Hospital, Quanzhou, China.
Clin Hemorheol Microcirc. 2018;70(1):51-58. doi: 10.3233/CH-170276.
Intracellular calcium overload has been implicated in various pathological conditions including ischemia reperfusion injury. This study aims to explore the effect and probable mechanism of dantrolene, a ryanodine receptor and intracellular calcium antagonist, on the skeletal muscle ischemia reperfusion injury.
SD rats were randomly divided into three groups: sham group which underwent anaesthesia and exposure of femoral vein, reperfusion group that received 2 h ischemia and the amount of diluent via femoral vein before 4 h reperfusion, dantrolene group that underwent 2 h ischemia and was given 2 mg/kg dantrolene via femoral vein before 4 h reperfusion. The parameters measured at the end of reperfusion included serum maleic dialdehyde (MDA), tissue myeloperoxidase (MPO) and muscle histology, as well as serum TNF-α and IL-10.
Levels of MDA, MPO and TNF-α increased in the reperfusion group, whereas the relevant expressions in the dantrolene group decreased significantly. Histological examination demonstrated significant improvements between the same both groups. IL-10 reflected the protection observed above with a significant up-regulation of expression after dantrolene administration.
Ryanodine receptor antagonist dantrolene exerted a significant protective effect against the inflammatory injury of skeletal muscle ischemia reperfusion. The underlying molecular mechanism is probably related to the suppression of TNF-α levels and the increment of IL-10 expression.
细胞内钙超载与包括缺血再灌注损伤在内的多种病理状况有关。本研究旨在探讨雷诺嗪受体及细胞内钙拮抗剂丹曲林对骨骼肌缺血再灌注损伤的影响及可能机制。
将SD大鼠随机分为三组：假手术组，仅接受麻醉及股静脉暴露；再灌注组，经历2小时缺血，于再灌注前4小时经股静脉给予一定量稀释剂；丹曲林组，经历2小时缺血，于再灌注前4小时经股静脉给予2mg/kg丹曲林。再灌注结束时检测的参数包括血清丙二醛（MDA）、组织髓过氧化物酶（MPO）及肌肉组织学，以及血清肿瘤坏死因子-α（TNF-α）和白细胞介素-10（IL-10）。
再灌注组MDA、MPO及TNF-α水平升高，而丹曲林组相关表达显著降低。组织学检查显示两组间有显著改善。IL-10反映了上述保护作用，丹曲林给药后其表达显著上调。
雷诺嗪受体拮抗剂丹曲林对骨骼肌缺血再灌注的炎症损伤具有显著保护作用。潜在的分子机制可能与抑制TNF-α水平及增加IL-10表达有关。
