New York, N.Y. From the Laboratory for Bioregenerative Medicine and Surgery, Department of Surgery, Weill Cornell Medical College.
Plast Reconstr Surg. 2010 Dec;126(6):1890-1898. doi: 10.1097/PRS.0b013e3181f446bc.
Recent evidence suggests that hydrogen sulfide is capable of mitigating the degree of cellular damage associated with ischemia-reperfusion injury. The purpose of this study was to determine whether it is protective in skeletal muscle.
This study used both in vitro (cultured myotubes subjected to sequential anoxia and normoxia) and in vivo (mouse hind-limb ischemia followed by reperfusion) models in which hydrogen sulfide (0 to 1000 μM) was delivered before the onset of oxygen deficiency. Injury score and apoptotic index were determined by analysis of specimens stained with hematoxylin and eosin and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, respectively.
In vitro, hydrogen sulfide reduced the apoptotic index by as much as 99 percent (p=0.001), with optimal protection conferred by raising intravascular hydrogen sulfide to 10 μM. In vivo, 10 μM hydrogen sulfide delivered before 3 hours of hind-limb ischemia followed by 3 hours of reperfusion resulted in protection against ischemia-reperfusion injury-induced cellular changes, as evidenced by significant decreases in injury score and apoptotic index (by as much as 91 percent; p=0.001). These findings were consistent at 4 weeks after injury and reperfusion.
These findings confirm that the preischemic delivery of hydrogen sulfide limits ischemia-reperfusion injury-induced cellular damage in myotubes and skeletal muscle and suggests that, when given in the appropriate dose, this molecule may have significant therapeutic applications in multiple clinical scenarios.
最近的证据表明，硫化氢能够减轻与缺血再灌注损伤相关的细胞损伤程度。本研究的目的是确定其在骨骼肌中是否具有保护作用。
本研究使用了体外（缺氧和正常氧培养的肌管）和体内（小鼠后肢缺血再灌注）模型，在缺氧开始前给予硫化氢（0 至 1000 μM）。通过苏木精和曙红染色分析标本和末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记法分别确定损伤评分和凋亡指数。
在体外，硫化氢将凋亡指数降低了多达 99%（p=0.001），通过将血管内硫化氢升高至 10 μM 可获得最佳保护。在体内，在 3 小时后肢缺血前给予 10 μM 硫化氢，然后再进行 3 小时的再灌注，可防止缺血再灌注损伤引起的细胞变化，这表现在损伤评分和凋亡指数显著降低（多达 91%；p=0.001）。这些发现与损伤和再灌注后 4 周时一致。
这些发现证实，缺血前给予硫化氢可限制肌管和骨骼肌中缺血再灌注损伤引起的细胞损伤，并表明在给予适当剂量时，该分子在多种临床情况下可能具有重要的治疗应用。
