Travis D L, Fabia R, Netto G G, Husberg B S, Goldstein R M, Klintmalm G B, Levy M F
Baylor University Medical Center, Transplant Services, Dallas, Texas 75246, USA.
J Surg Res. 1998 Mar;75(2):116-26. doi: 10.1006/jsre.1998.5297.
Cyclosporine A (CYA) is primarily utilized as an immunosuppressant, but its mechanisms of action (including decreased neutrophilic free radical production and stabilization of mitochondrial and lysosomal membranes) may have beneficial effects in ischemia and reperfusion (IR) injury. This study was undertaken to examine the effect of CYA pretreatment on porcine liver histopathologic changes and enzymatic release caused by ischemia and reperfusion.
CYA was administered orally for 4 days prior to surgery in two doses (10 or 20 mg/kg) while controls received only the control vehicle. Pigs were then exposed to 4 h of hepatic ischemia followed by 2 h of reperfusion.
Significant decreases in AST levels compared to controls were seen in high dose CYA pigs at the end of ischemia and at 30-min intervals during the reperfusion period. Controls exhibited necrotic hepatocytes and severe inflammatory cell infiltration, while high dose CYA animals demonstrated mild inflammatory cell infiltrates. Controls had decreased survival--20% did not survive reperfusion.
This study indicates that CYA may be useful in decreasing initial damage resulting from warm hepatic IR injury.
环孢素A（CYA）主要用作免疫抑制剂，但其作用机制（包括减少中性粒细胞自由基生成以及稳定线粒体和溶酶体膜）可能对缺血再灌注（IR）损伤具有有益作用。本研究旨在探讨CYA预处理对猪肝脏缺血再灌注所致组织病理学变化和酶释放的影响。
手术前4天，以两种剂量（10或20mg/kg）口服CYA，而对照组仅接受对照载体。然后使猪经历4小时的肝脏缺血，随后再灌注2小时。
在缺血结束时以及再灌注期间每隔30分钟，高剂量CYA组猪的AST水平与对照组相比显著降低。对照组出现坏死肝细胞和严重的炎性细胞浸润，而高剂量CYA组动物表现为轻度炎性细胞浸润。对照组生存率降低——20%未存活至再灌注结束。
本研究表明CYA可能有助于减少温热性肝脏IR损伤所致的初始损伤。
