Sirtuin 2 Regulates Microvascular Inflammation during Sepsis.
Sirtuin 2 Regulates Microvascular Inflammation during Sepsis.
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DOI：
10.1155/2017/2648946
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发表时间：
2017
影响因子：
4.1
通讯作者：
Vachharajani V
中科院分区：
文献类型：
--
作者：
Buechler N;Wang X;Yoza BK;McCall CE;Vachharajani V
目标。败血症和感染性休克是非冠状动脉重症监护病房的主要死亡原因，仅在美国每年就导致20多万人死亡。循环细胞-内皮细胞的相互作用是脓毒症炎症的速率决定因素。Sirtuin是一个由七个成员组成的蛋白质家族(SIRT1-7)，它在表观遗传上控制炎症。我们已经研究了SIRT 1、3和6在脓毒症中的作用。在这个项目中，我们研究了SIRT2在脓毒症相关炎症中的作用。方法：研究方法。采用盲肠结扎穿孔(CLP)方法建立C57BL/6(WT)、SIRT2基因敲除(SIRT2KO)和SIRT2高表达(SIRT2KI)小鼠脓毒症模型。采用活体显微镜观察白细胞/血小板黏附，免疫组织化学(IHC)观察CLP/Sham术后6h小肠E-选择素/ICAM-1黏附分子表达。我们还研究了WT、SIRT2KO和SIRT2KI脓毒症小鼠的7天存活率。结果。与WT小鼠相比，SIRT2KO小鼠表现出夸张的表现，而SIRT2KI小鼠表现出细胞粘附性的减弱，并伴有败血症。我们还发现，与WT脓毒症小鼠相比，SIRT2KO小鼠小肠E-选择素和ICAM-1的表达增加，而SIRT2KI小鼠的表达降低。我们发现，SIRT2KO组小鼠的7天存活率降低，而SIRT2KI脓毒症小鼠的7天存活率增加。结论。SIRT2调节脓毒症的微血管炎症并影响生存。
Objective. Sepsis and septic shock, the leading causes of death in noncoronary intensive care units, kill more than 200,000/year in the US alone. Circulating cell-endothelial cell interactions are the rate determining factor in sepsis inflammation. Sirtuin, a seven-member family of proteins (SIRT1–7), epigenetically controls inflammation. We have studied the roles of SIRTs 1, 3, and 6 in sepsis previously. In this project, we studied the role of SIRT2 on sepsis-related inflammation. Methods. Sepsis was induced in C57Bl/6 (WT), SIRT2 knockout (SIRT2KO), and SIRT2 overexpressing (SIRT2KI) mice by cecal ligation and puncture (CLP). We studied leukocyte/platelet adhesion using intravital microscopy and E-selectin/ICAM-1 adhesion molecule expression in the small intestine with immunohistochemistry (IHC) six hours post-CLP/sham surgery. We also studied 7-day survival rates in WT, SIRT2KO, and SIRT2KI sepsis mice. Results. Compared to WT mice, SIRT2KO mice show exaggeration while SIRT2KI mice show attenuation of cellular adhesion with sepsis in the small intestine. We also show that the small intestinal E-selectin and ICAM-1 expressions increased in SIRT2KO and decreased in SIRT2KI mice versus those in WT sepsis mice. We show that the 7-day survival rate is decreased in SIRT2KO and increased in SIRT2KI sepsis mice. Conclusion. SIRT2 modulates microvascular inflammation in sepsis and affects survival.