Cells:研究揭示重组人肝脏再生增强剂对缺血再灌注所致有害过程的影响

2020-03-18 MedSci原创 MedSci原创

肝缺血再灌注损伤(IRI)是肝脏切除和移植的主要并发症。在这里,我们分析了重组人肝脏再生增强剂(rALR)(一种抗氧化和抗凋亡蛋白)对缺血再灌注(IR)所致有害过程的影响。

肝缺血再灌注损伤(IRI)是肝脏切除和移植的主要并发症。在这里,我们分析了重组人肝脏再生增强剂(rALR)(一种抗氧化和抗凋亡蛋白)对缺血再灌注(IR)所致有害过程的影响。

 

rALR可减少小鼠IRI模型中的组织损伤(坏死),脂质过氧化水平(氧化应激)和抗氧化基因的表达。损伤相关分子模式(DAMP)和炎性细胞因子,例如HMGB1和TNFα,不受rALR的影响。此外,我们评估了IRI后炎性细胞向肝组织的浸润,发现CD3或γδTCR阳性细胞没有变化,γδTCR细胞没有表达IL17 /IFNγ。

 

在rALR治疗的小鼠中,Gr-1阳性细胞(嗜中性粒细胞)的数量以及髓过氧化物酶活性较低。此外,我们发现在缺氧条件下,经过LR26处理的RAW264.7细胞和原代小鼠肝细胞中的ROS水平会降低。rALR的应用还导致肝细胞中化学吸引剂(如CXCL1,CXCL2和CCl2)的表达降低。另外,IR小鼠肝脏3小时后和人肝移植的活检组织中ALR表达增加,而组织损伤的迹象最小。

 

因此,ALR通过减少由关键肝趋化因子的较低表达和ROS生成介导的嗜中性白细胞组织浸润来减弱IRI。

 

原始出处:

 

Thomas S. WeissMadeleine Lupke, et al., Augmenter of Liver Regeneration Reduces Ischemia Reperfusion Injury by Less Chemokine Expression, Gr-1 Infiltration and Oxidative Stress. Cells. 2019 Nov; 8(11): 1421. doi: 10.3390/cells8111421

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    2020-10-21 docwu2019
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