Matsumoto Tadashi, O'Malley Kerri, Efron Philip A, Burger Colette, McAuliffe Priscilla F, Scumpia Philip O, Uchida Takefumi, Tschoeke Sven K, Fujita Shiro, Moldawer Lyle L, Hemming Alan W, Foley David P
Department of Surgery, University of Florida College of Medicine, Gainesville, FL, USA, and Department of Surgery, Showa University Fujigaoka Hospital, Yokohama, Japan.
Surgery. 2006 Nov;140(5):793-802. doi: 10.1016/j.surg.2006.04.010. Epub 2006 Aug 23.
Ischemic preconditioning has been shown to protect the liver from ischemia/reperfusion injury. We hypothesized that IL-6 directly modulates the protective effects of ischemic preconditioning.
Three weeks after undergoing splenic transposition, wild-type C57BL/6 and IL-6 null mice underwent 75 minutes of total hepatic ischemia with or without prior ischemic preconditioning (10 minutes of ischemia followed by 15 minutes of reperfusion). After reperfusion, serum ALT, serum IL-6, hepatic IL-6 mRNA, hepatic pSTAT3, and liver histology were evaluated.
In wild-type mice, survival at 24 hours was greater in the preconditioned group compared with the non-preconditioned group (75% vs 40%, P<.05). In IL-6 null mice, however, ischemic preconditioning did not improve survival when compared with the non-preconditioned group. Preconditioning significantly reduced hepatocellular injury in wild-type mice (P<.05) when compared with IL-6 null animals. This protection was associated with significant increases in serum IL-6, hepatic IL-6 mRNA, and hepatic pSTAT3 levels (P<.05). The protective effects of ischemic preconditioning that correlated with significant increases in systemic IL-6, hepatic IL-6 mRNA abundance, and pSTAT3 levels, were not observed in IL-6 null mice.
The protective effects of ischemic preconditioning during total hepatic ischemia/reperfusion injury are dependent on IL-6 signaling and are associated with increased phosphorylation of hepatic STAT3.
缺血预处理已被证明可保护肝脏免受缺血/再灌注损伤。我们推测白细胞介素-6（IL-6）直接调节缺血预处理的保护作用。
在进行脾转位三周后，野生型C57BL/6小鼠和IL-6基因敲除小鼠接受75分钟的全肝缺血，有无预先缺血预处理（10分钟缺血后再灌注15分钟）。再灌注后，评估血清谷丙转氨酶（ALT）、血清IL-6、肝脏IL-6信使核糖核酸（mRNA）、肝脏磷酸化信号转导子和转录激活子3（pSTAT3）以及肝脏组织学。
在野生型小鼠中，预处理组24小时生存率高于未预处理组（75%对40%，P<0.05）。然而，在IL-6基因敲除小鼠中，与未预处理组相比，缺血预处理并未提高生存率。与IL-6基因敲除动物相比，预处理显著降低了野生型小鼠的肝细胞损伤（P<0.05）。这种保护作用与血清IL-6、肝脏IL-6 mRNA和肝脏pSTAT3水平的显著升高相关（P<0.05）。在IL-6基因敲除小鼠中未观察到缺血预处理的保护作用与全身IL-6、肝脏IL-6 mRNA丰度和pSTAT3水平的显著升高相关。
全肝缺血/再灌注损伤期间缺血预处理的保护作用依赖于IL-6信号传导，并与肝脏信号转导子和转录激活子3（STAT3）磷酸化增加有关。
