Propofol postconditioning attenuates hippocampus ischemia-reperfusion injury via modulating JAK2/STAT3 pathway in rats after autogenous orthotropic liver transplantation
Propofol postconditioning attenuates hippocampus ischemia-reperfusion injury via modulating JAK2/STAT3 pathway in rats after autogenous orthotropic liver transplantation
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DOI：
10.1016/j.brainres.2016.12.015
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发表时间：
2017-02-15
期刊：
影响因子：
2.9
通讯作者：
Yu Wenli
中科院分区：
文献类型：
--
作者：
Jia Lili;Wang Fei;Yu Wenli
肝移植已成为终末期肝病的常规治疗方法。移植手术过程中可能会发生循环系统和内环境的剧烈变化，导致包括脑在内的多个器官损伤。与肝移植相关的脑损伤的具体机制尚未阐明。前期研究表明，JAK/STAT信号转导通路参与中枢神经系统的发育，如神经细胞的增殖、存活、分化等，并且在疾病过程中也发挥作用，包括脑肿瘤、脑缺血等中枢神经系统疾病。在本研究中，我们探讨异丙酚是否通过JAK2/STAT3通路在保护海马中发挥重要作用。将 32 只健康雄性 SpragueDawley 大鼠随机分为四组 (n = 8)。假手术组(S组)、自体正向肝移植组(I组)、自体正向肝移植+丙泊酚治疗组(P组)和自体正向肝移植+丙泊酚+AG490治疗组(A组)。我们使用 HE 染色、光学显微镜、实时 PCR 和蛋白质印迹评估了海马的组织学损伤、炎症、氧化应激和细胞凋亡。结果显示，与假手术组相比，I组海马出现明显损伤，血清S100β、NSE水平升高，组织学改变。然而，异丙酚的诱导降低了MDA、TNFα、S100β、NSE的水平，增加了SOD、IL-10的活性，同时减弱了JAK2和STAT3的表达。一致地，用 JAK2/STAT3 通路抑制剂 AG490 预处理，降低了 MDA、TNF α、S100 β、NSE 的水平，增加了 SOD、IL-10 的活性，并减弱了 JAK2 和 STAT3 的表达。这些结果表明，自体正交异性肝移植诱导海马JAK2/STAT3信号通路的激活。丙泊酚预处理可减轻自体正交异性肝移植通过 JAK2/STAT3 途径诱导的海马损伤。 (C) 2016 Elsevier B.V. 保留所有权利。
Liver transplantation has been a routine treatment for the end stage liver diseases. Severe changes in circulation system and internal environment may occur during transplant surgery and cause injury to many organs including brain. Specific mechanisms of brain injury associated with liver transplantation are not yet elucidated. Previous studies have shown that the JAK/STAT signal transduction pathways are involved in the development of the central nervous system, such as nerve cell proliferation, survival, differentiation, and it also have a role in the disease processes, including brain tumor, brain ischemia and other diseases of the central nervous system. In this study we investigate whether propofol plays an important role in protecting the hippocampus through JAK2/STAT3 pathway. Thirty-two healthy male SpragueDawley rats, were randomly divided into four groups (n = 8). Sham operation group (group S), autogenous orthotropic liver transplantation group (group I), autogenous orthotropic liver transplantation + propofol treatment group (group P) and autogenous orthotropic liver transplantation + propofol + AG490 treatment group (group A). We evaluated histological damage, inflammation, oxidative stress and apoptosis in hippocampus using HE staining, light microscope, real-time PCR and western blot. The results showed that there was a significant damage of hippocampus in group I compared to the sham group as demonstrated by increased serum levels of S100 beta, NSE and the histological changes. However, an induction of propofol reduced the levels of MDA, TNF alpha, S100 beta, NSE and increased activity of SOD, IL-10, and attenuated the expression ofJAK2 and STAT3, meanwhile. Consistently, pretreatment with JAK2/STAT3 pathway inhibitor AG490, decreased the levels of MDA, TNF alpha, S100 beta, NSE and increased activity of SOD, IL-10, and attenuated the expression of JAK2 and STAT3. These results reveal that autogenous orthotropic liver transplantation induces the activation of JAK2/STAT3 signaling pathway in hippocampus. Pretreatment with propofol attenuates autogenous orthotropic liver transplantation induces hippocampal injury via JAK2/STAT3 pathway. (C) 2016 Elsevier B.V. All rights reserved.