Yamamura Mitsuhiro, Miyamoto Yuji, Mitsuno Masataka, Tanaka Hiroe, Ryomoto Masaaki, Fukui Shinya
Department of Cardiovascular Surgery, Hyogo College of Medicine, Hyogo, Japan.
Int J Angiol. 2013 Dec;22(4):267-70. doi: 10.1055/s-0033-1357261.
It is well known that free radicals cause reperfusion injury following leg ischemia. We showed that the free radical scavenger, edaravone (Radicut, Mitsubishi Tanabe Pharma Co., Osaka, Japan), might suppress reperfusion injury in rat. In this study, we used transmission electron microscope (TEM) to investigate how edaravone suppresses reperfusion injury by focusing on glycogen granules in the lower extremity muscles. Male Lewis rats (582 ± 35 g) were intraperitoneally injected with edaravone (3.0 mg/kg, edaravone group, n = 5) or the same dose of saline (control group, n = 5). The rat reperfusion injury models were induced by clamping the bilateral common femoral arteries for 5 hours and then declamping. The muscles were harvested at 5 hours after the start of reperfusion. Under a TEM (JEM-1220, Nippon Denshi Co., Tokyo, Japan), we counted the number of glycogen granules at ×50,000 magnification on each five different fields. The TEM sections from the control group showed a marked loss of glycogen granules and swollen mitochondria. In contrast, the TEM sections from the edaravone group showed numerous glycogen granules and normal mitochondria. The mean density of glycogen granules in the edaravone group was significantly higher than that in the control group (88.5 ± 5.3 vs. 16.4 ± 3.1 particles/µm(2), p < 0.001). Our TEM results confirmed that edaravone suppresses reperfusion injury following leg ischemia by maintaining the glycogen granules in muscles.
众所周知，自由基会导致腿部缺血后的再灌注损伤。我们发现自由基清除剂依达拉奉（Radicut，日本大阪三菱田边制药公司）可能会抑制大鼠的再灌注损伤。在本研究中，我们使用透射电子显微镜（TEM），通过关注下肢肌肉中的糖原颗粒来研究依达拉奉如何抑制再灌注损伤。雄性Lewis大鼠（582±35克）腹腔注射依达拉奉（3.0毫克/千克，依达拉奉组，n = 5）或相同剂量的生理盐水（对照组，n = 5）。通过夹闭双侧股总动脉5小时然后松开夹闭来诱导大鼠再灌注损伤模型。在再灌注开始后5小时采集肌肉。在透射电子显微镜（JEM - 1220，日本东京日本电子株式会社）下，我们在五个不同视野中以×50,000放大倍数计数糖原颗粒的数量。对照组的透射电镜切片显示糖原颗粒明显减少且线粒体肿胀。相比之下，依达拉奉组的透射电镜切片显示有大量糖原颗粒且线粒体正常。依达拉奉组糖原颗粒的平均密度显著高于对照组（88.5±5.3对16.4±3.1个颗粒/μm²，p < 0.001）。我们的透射电镜结果证实，依达拉奉通过维持肌肉中的糖原颗粒来抑制腿部缺血后的再灌注损伤。
