Bongiovanni Dario, Ziegler Tilman, D'Almeida Sascha, Zhang Tianqiong, Ng Judy K M, Dietzel Steffen, Hinkel Rabea, Kupatt Christian
Klinikum der Universität München, Medizinische Klinik und Poliklinik I , Marchioninistr. 15, 81377 Munich , Germany +49 89 44007 3075 ; +49 89 44007 6075 ;
Expert Opin Biol Ther. 2015;15 Suppl 1:S203-10. doi: 10.1517/14712598.2015.1006193. Epub 2015 Jan 21.
The actin polymerization regulator Thymosin β4 (Tβ4) has been shown to be involved in angiogenesis, wound healing, cell survival and anti-inflammatory responses. We have previously shown that Tβ4 is capable of recruiting pericytes, thus stabilizing the endothelial barrier function. Here, we analyzed whether treatment with Tβ4 is able to reduce the pericytes loss in lipopolysaccharides (LPS)-induced sepsis and to improve the hemodynamic function and survival in C57BL/6 mice.
Fourteen days before LPS injection, the mice were injected with an adeno-associated virus carrying the Tβ4 (rAAV.Tβ4) or LacZ gene (rAAV.LacZ). A sepsis-severity score was assessed, and non-invasive hemodynamic and permeability measurements were performed. Heart and muscle samples were analyzed for PECAM-1(+) capillaries and NG2(+)pericytes.
At 36 h, there was a decrease of sepsis severity score in rAAV.Tβ4-treated animals as compared to rAAV.LacZ-treated control. rAAV.Tβ4-treated animals displayed lower perivascular leakage and higher blood pressure compared to control. Of note, the rAAV.Tβ4 group showed a higher pericyte count in heart and peripheral muscle samples. Finally, Tβ4-treatment reduced mortality compared to control.
The data indicate a preventive role of Tβ4 in septic hypercirculation and highlight Tβ4 as a potential therapeutic target in severe sepsis.
肌动蛋白聚合调节剂胸腺素β4（Tβ4）已被证明参与血管生成、伤口愈合、细胞存活和抗炎反应。我们之前已经表明，Tβ4能够募集周细胞，从而稳定内皮屏障功能。在此，我们分析了用Tβ4治疗是否能够减少脂多糖（LPS）诱导的脓毒症中周细胞的损失，并改善C57BL/6小鼠的血流动力学功能和存活率。
在注射LPS前14天，给小鼠注射携带Tβ4（rAAV.Tβ4）或LacZ基因（rAAV.LacZ）的腺相关病毒。评估脓毒症严重程度评分，并进行非侵入性血流动力学和通透性测量。分析心脏和肌肉样本中的PECAM-1（+）毛细血管和NG2（+）周细胞。
在36小时时，与rAAV.LacZ处理的对照组相比，rAAV.Tβ4处理的动物脓毒症严重程度评分降低。与对照组相比，rAAV.Tβ4处理的动物血管周围渗漏更低，血压更高。值得注意的是，rAAV.Tβ4组在心脏和外周肌肉样本中显示出更高的周细胞计数。最后，与对照组相比，Tβ4治疗降低了死亡率。
数据表明Tβ4在脓毒症性高循环中具有预防作用，并突出了Tβ4作为严重脓毒症潜在治疗靶点的地位。
