Department of Anesthesiology, SUNY-Downstate Medical Center, Brooklyn, NY 11203, United States.
Mol Immunol. 2013 Dec;56(4):507-12. doi: 10.1016/j.molimm.2013.05.001. Epub 2013 Aug 1.
Loss of plasma membrane integrity (LPMI) is a hallmark of necrotic cell death. The involvement of complement and ROS in the development of LPMI during the early stages of murine myocardial ischemia-reperfusion injury was investigated. LPMI developed within 1 h of reperfusion to a level that was sustained through 24 h. C3 deposition became significant at 3-h reperfusion and thus contributed little to LPMI prior to this time. SOD1 transgenic mice had significantly less LPMI compared with WT mice at 1 h of reperfusion but not at later time points. Catalase transgenic mice were not protected from LPMI at 1-h reperfusion compared with WT mice, but had 69% less LPMI at 3-h reperfusion. This protection was transient. At 24-h reperfusion the LPMI of catalase transgenic mice was identical to that of WT mice. The delayed benefits of over-expressed catalase compared with SOD1 are consistent with its antioxidant action downstream of SOD1. The onset of LPMI occurs within 1 h of reperfusion at a level that is maintained through 24 h. ROS contribute significantly to LPMI during the first 3 h of reperfusion, while complement deposition, which becomes significant after 3-h reperfusion, may contribute thereafter.
细胞膜完整性丧失（LPMI）是坏死性细胞死亡的标志。本研究旨在探讨补体和 ROS 在鼠心肌缺血再灌注损伤早期 LPMI 发展中的作用。LPMI 在再灌注后 1 小时内发展到持续 24 小时的水平。C3 沉积在再灌注 3 小时时变得显著，因此在此之前对 LPMI 的贡献不大。与 WT 小鼠相比，SOD1 转基因小鼠在再灌注 1 小时时 LPMI 明显减少，但在稍后的时间点则没有。与 WT 小鼠相比，过氧化氢酶转基因小鼠在再灌注 1 小时时未免受 LPMI 的影响，但在再灌注 3 小时时 LPMI 减少了 69%。这种保护是短暂的。在再灌注 24 小时时，过氧化氢酶转基因小鼠的 LPMI 与 WT 小鼠相同。与 SOD1 相比，过表达过氧化氢酶的延迟益处与其在 SOD1 下游的抗氧化作用一致。LPMI 在再灌注后 1 小时内发生，水平持续 24 小时。ROS 在再灌注的前 3 小时内对 LPMI 有重要贡献，而在再灌注 3 小时后变得显著的补体沉积此后可能会有贡献。
