Wang Xin-Tao, Tian Ye, Xu Wen-Xiao, Cui Li-Huang, Xiang Shou-Yang, Lü Song-Cen
-Affiliated Hospital of Harbin medical University, Harbin, China.
Cell Physiol Biochem. 2015;37(2):465-76. doi: 10.1159/000430369. Epub 2015 Aug 28.
BACKGROUND/AIM: Ischemia/reperfusion (I/R) injury of skeletal muscles is common pathophysiology during surgeries and the superoxide dismutase (SOD) plays a critical role in this process. SOD-modeled coordination compound (MSODa) may simulate the protective effects as SOD.
Therefore, this study was designed to explore the protective effects and underlying mechanism of MSODa on malondialdehyde (MDA) and integrin-β2 (CD11b/CD18) in plasma, myeloperoxidase (MPO) and intercellular cell adhesion molecule-1 (ICAM-1) in tissue, and morphological changes before and after I/R injury. The rat model of I/R in hind limb was established and randomly divided into sham, ischemia, I/R, I/R-treated with saline, SOD, and MSODa, respectively.
These results showed that averaged values for MDA, MPO, CD11b/CD18, and ICAM-1 were significantly increased (P < 0.01 vs ischemia alone) in a time-dependent fashion along with marked tissue remodeling, such as abnormal arrangement of muscular fibers, interstitial edema, vasodilation with no-reflow, inflammatory cells adherent and infiltration, structural changes in mitochondrial, and decrease in glycogens as well. However, all parameter changes induced by I/R injury were reversed, at least partially, by MSODa and SOD treatments and intriguingly, the beneficial/protective effects of MSODa was superior to SOD with an early onset.
This novel finding demonstrates that MSODa improves I/R injury of skeletal muscles due at least partially to inhibition of adherent molecule expression and reduction of oxygen free radical formation during I/R pathophysiological processes and this protective action of MSODa was superior to SOD, highlighting the bright future for MSODa in clinical management of tissue I/R injury.
背景/目的:骨骼肌缺血/再灌注(I/R)损伤是手术过程中常见的病理生理过程,超氧化物歧化酶(SOD)在此过程中起关键作用。SOD模拟配位化合物(MSODa)可能具有与SOD相似的保护作用。
因此,本研究旨在探讨MSODa对血浆中丙二醛(MDA)和整合素-β2(CD11b/CD18)、组织中髓过氧化物酶(MPO)和细胞间黏附分子-1(ICAM-1)的保护作用及其潜在机制,以及I/R损伤前后的形态学变化。建立大鼠后肢I/R模型,并随机分为假手术组、缺血组、I/R组、生理盐水处理的I/R组、SOD组和MSODa组。
这些结果表明,MDA、MPO、CD11b/CD18和ICAM-1的平均值随时间呈依赖性显著升高(与单独缺血组相比,P<0.01),同时伴有明显的组织重塑,如肌纤维排列异常、间质水肿、无复流性血管扩张、炎性细胞黏附和浸润、线粒体结构改变以及糖原减少。然而,I/R损伤引起的所有参数变化均被MSODa和SOD治疗至少部分逆转,有趣的是,MSODa的有益/保护作用优于SOD,且起效较早。
这一新颖的发现表明,MSODa改善骨骼肌I/R损伤至少部分归因于其在I/R病理生理过程中抑制黏附分子表达和减少氧自由基形成,且MSODa的这种保护作用优于SOD,凸显了MSODa在组织I/R损伤临床管理中的光明前景。