Bender B, Baranyi M, Kerekes A, Bodrogi L, Brands R, Uhrin P, Bösze Z
Rabbit Genome and Biomodel Group, NARIC-Agricultural Biotechnology Institute, Gödöllő, Hungary.
Physiol Res. 2015;64(5):731-8. doi: 10.33549/physiolres.932946. Epub 2015 Mar 24.
Sepsis is a life threatening condition that arises when the body's response to an infection injures its own tissues and organs. Sepsis can lead to shock, multiple organ failure and death especially if not recognized early and treated promptly. Molecular mechanisms underlying the systemic inflammatory response syndrome associated with sepsis are still not completely defined and most therapies developed to target the acute inflammatory component of the disease are insufficient. In this study we investigated a possibility of combating sepsis in a mouse model by intravenous treatment with recombinant human tissue non-specific alkaline phosphatase (rhTNAP) derived from transgenic rabbit milk. We induced sepsis in mice by intraperitoneal injection of LPS and three hours later treated experimental group of mice by intravenous injection with rhTNAP derived from transgenic rabbits. Such treatment was proved to be physiologically effective in this model, as administration of recombinant rhTNAP successfully combated the decrease in body temperature and resulted in increased survival of mice (80 % vs. 30 % in a control group). In a control experiment, also the administration of bovine intestinal alkaline phosphatase by intravenous injection proved to be effective in increasing survival of mice treated with LPS. Altogether, present work demonstrates the redeeming effect of the recombinant tissue non-specific AP derived from milk of genetically modified rabbits in combating sepsis induced by LPS.
脓毒症是一种危及生命的病症，当身体对感染的反应损伤自身组织和器官时就会出现。脓毒症可导致休克、多器官功能衰竭和死亡，尤其是如果不及早识别和及时治疗。与脓毒症相关的全身炎症反应综合征的分子机制仍未完全明确，并且针对该疾病急性炎症成分开发的大多数疗法都不足。在本研究中，我们调查了通过静脉注射源自转基因兔奶的重组人组织非特异性碱性磷酸酶（rhTNAP）在小鼠模型中对抗脓毒症的可能性。我们通过腹腔注射LPS在小鼠中诱导脓毒症，三小时后通过静脉注射源自转基因兔的rhTNAP对实验组小鼠进行治疗。在该模型中，这种治疗被证明具有生理有效性，因为重组rhTNAP的给药成功对抗了体温下降并提高了小鼠的存活率（80% 对比对照组的30%）。在对照实验中，静脉注射牛肠碱性磷酸酶也被证明可有效提高接受LPS治疗的小鼠的存活率。总之，目前的工作证明了源自转基因兔奶的重组组织非特异性碱性磷酸酶在对抗LPS诱导的脓毒症中的挽救作用。
