Role for the alternative complement pathway in ischemia/reperfusion injury
Role for the alternative complement pathway in ischemia/reperfusion injury
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DOI：
10.1016/s0002-9440(10)63839-4
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发表时间：
2003-02-01
影响因子：
6
通讯作者：
Zhao, H
中科院分区：
文献类型：
--
作者：
Stahl, GL;Xu, YY;Zhao, H
补体终末成分在介导大鼠和小鼠缺血再灌注损伤后的组织损伤中起重要作用。然而，参与I/R损伤的特异性补体途径尚不清楚。旁路途径在I/R损伤中的作用可能特别重要，因为它放大了补体激活和沉积。在这项研究中，替代途径在I/R损伤的作用进行了评估，使用因子D缺陷（-/-）和杂合子（+/-）小鼠。通过夹闭肠系膜动脉20分钟，然后再灌注3小时来诱导胃肠缺血（GI）。假手术对照小鼠（+/-vs-/-）具有相似的基线肠乳酸脱氢酶活性（P = ns）。GI/R后，-/-小鼠的肠乳酸脱氢酶活性高于+/-小鼠（P = 0.02），从而证明了-/-小鼠的保护作用。GI/R后+/-小鼠肠髓过氧化物酶活性显著高于-/-小鼠（P <0.001）。GI/R后+/-小鼠的肺髓过氧化物酶活性显著高于-/-小鼠（P = 0.03）。向动物中添加人因子D可恢复GI/R损伤，并可通过抗人因子D的功能抑制性抗体进行预防。提示补体旁路途径在胃肠道/再灌注后局部和远端组织损伤中起重要作用。抑制因子D可能代表GI/R损伤的有效治疗方法。
The terminal complement components play an important role in mediating tissue injury after ischemia and reperfusion (I/R) injury in rats and mice. However, the specific complement pathways involved in I/R injury are unknown. The role of the alternative pathway in I/R injury may be particularly important, as it amplifies complement activation and deposition. In this study, the role of the alternative pathway in I/R injury was evaluated using factor D-deficient (-/-) and heterozygote (+/-) mice. Gastrointestinal ischemia (GI) was induced by clamping the mesenteric artery for 20 minutes and then reperfused for 3 hours. Sham-operated control mice (+/- versus -/-) had similar baseline intestinal lactate dehydrogenase activity (P = ns). intestinal lactate dehydrogenase activity was greater in -/- mice compared to +/- mice after GI/R (P = 0.02) thus demonstrating protection in the -/- mice. Intestinal myeloperoxidase activity in +/- mice was significantly greater than -/- mice after GI/R (P < 0.001). Pulmonary myeloperoxidase activity after GI/R was significantly higher in +/- than -/- mice (P = 0.03). Addition of human factor D to animals restored GI/R injury and was prevented by a functionally inhibitory antibody against human factor D. These data suggest that the alternative complement pathway plays an important role in local and remote tissue injury after GI/R. Inhibition of factor D may represent an effective therapeutic approach for GI/R injury.