Engles R E, Huber T S, Zander D S, Hess P J, Welborn M B, Moldawer L L, Seeger J M
Department of Surgery, University of Florida College of Medicine, Gainesville 32610-0286, USA.
J Surg Res. 1997 May;69(2):425-8. doi: 10.1006/jsre.1997.5109.
Proinflammatory cytokines have been found to mediate part of the local and distant organ injury after ischemia and reperfusion (I/R). The anti-inflammatory cytokine interleukin-10 (IL-10) inhibits both TNF-alpha and IL-1, and we hypothesized that exogenous human IL-10 may decrease lung and soleus muscle injury after hindlimb I/R. Male Sprague-Dawley rats were randomly assigned to I/R (n = 10); I/R+IL-10 (10 micrograms i.v., n = 10), SHAM (n = 4); or SHAM+IL-10 (10 micrograms i.v., n = 4). Bilateral hindlimb ischemia was produced by tourniquet occlusion for 4 hr and all animals were sacrificed after 4 hr of reperfusion or at comparable times for the SHAMs. Soleus muscle cellular injury was determined by uptake of 99Tc pyrophosphate while soleus muscle capillary permeability, and lung capillary permeability were assessed by uptake of 125I-labeled albumin. Soleus muscle and lung neutrophil infiltration were measured with the myeloperoxidase assay. Serum samples were assessed for TNF-alpha production with the WEHI bioassay. Hindlimb I/R caused significant soleus muscle cellular injury, soleus muscle capillary injury, lung capillary injury, and lung neutrophil infiltration, Pretreatment with exogenous IL-10 significantly reduced soleus muscle capillary permeability and also reduced soleus muscle cellular injury, but not to a statistically significant degree. IL-10 administration also reduced pulmonary capillary permeability despite significantly increased lung neutrophil infiltration. Elevated TNF-alpha levels were found in 66% (4/6) rats in the I/R group versus 30% (3/10) rats in the I/R+IL-10 group. Exogenous IL-10 attenuates both local and distant organ injury after hindlimb I/R potentially independent of neutrophil infiltration.
促炎细胞因子已被发现介导缺血再灌注（I/R）后局部和远处器官损伤的部分过程。抗炎细胞因子白细胞介素-10（IL-10）可抑制肿瘤坏死因子-α（TNF-α）和白细胞介素-1（IL-1），我们推测外源性人IL-10可能会减轻后肢I/R后肺和比目鱼肌的损伤。雄性Sprague-Dawley大鼠被随机分为I/R组（n = 10）；I/R + IL-10组（静脉注射10微克，n = 10），假手术组（n = 4）；或假手术 + IL-10组（静脉注射10微克，n = 4）。通过止血带阻断造成双侧后肢缺血4小时，所有动物在再灌注4小时后或假手术组的相应时间点处死。通过99Tc焦磷酸盐摄取来确定比目鱼肌细胞损伤，而比目鱼肌毛细血管通透性和肺毛细血管通透性则通过125I标记白蛋白的摄取来评估。用髓过氧化物酶测定法测量比目鱼肌和肺中的中性粒细胞浸润。用WEHI生物测定法评估血清样本中TNF-α的产生。后肢I/R导致比目鱼肌细胞显著损伤、比目鱼肌毛细血管损伤、肺毛细血管损伤和肺中性粒细胞浸润，外源性IL-10预处理显著降低了比目鱼肌毛细血管通透性，也减轻了比目鱼肌细胞损伤，但未达到统计学显著程度。尽管肺中性粒细胞浸润显著增加，但给予IL-10也降低了肺毛细血管通透性。I/R组66%（4/6）的大鼠TNF-α水平升高，而I/R + IL-10组为30%（3/10）的大鼠。外源性IL-10可减轻后肢I/R后局部和远处器官的损伤，这可能与中性粒细胞浸润无关。
