Ann Surg:宿主防御肽在出血性休克中的保护作用

2017-03-23 MedSci MedSci原创

出血性休克(HS)是严重受伤患者死亡的常见原因。目前,尚无具体的疗法以降低HS相关的多器官功能衰竭(MOF)。近期,一项发表在杂志Ann Surg上的研究旨在评估:(1)创伤和HS患者宿主防御/抗菌肽LL-37的水平;(2)合成宿主抗原肽以及Pep19-4LF对HS相关的MOF的作用。研究者们首先测量了入住城市重大创伤中心的47例创伤/ HS患者的LL-37水平。 随后使用雄性Wistar大鼠进行

出血性休克(HS)是严重受伤患者死亡的常见原因。目前,尚无具体的疗法以降低HS相关的多器官功能衰竭(MOF)。


近期,一项发表在杂志Ann Surg上的研究旨在评估:(1)创伤和HS患者宿主防御/抗菌肽LL-37的水平;(2)合成宿主抗原肽以及Pep19-4LF对HS相关的MOF的作用。

研究者们首先测量了入住城市重大创伤中心的47例创伤/ HS患者的LL-37水平。 随后使用雄性Wistar大鼠进行HS(90分钟,目标平均动脉压:27-32mmHg)或假手术出来。复苏后的大鼠用Pep19-4LF [66(n = 8)或333μg/ kg·h(n = 8)]或载体(n = 12)处理4小时。

此项研究结果显示:与健康者相比,创伤/ HS患者血浆LL-37高出12倍。相对于使用载体处理的HS大鼠,用Pep19-4LF(高剂量)治疗的HS大鼠在4小时复苏期结束时具有较高的平均动脉压(79±4 vs 54±5mmHg),较少的肾功能障碍、肝损伤和肺部炎症反应。 Pep19-4LF增强(肾/肝)蛋白激酶B和内皮一氧化氮合酶磷酸化。Pep19-4LF减弱了HS诱导的p65从细胞质向细胞核中的迁移,Ser的IκB激酶的磷酸化以及Ser的IκBα磷酸化,导致核因子κB的抑制和促炎因子的形成。 Pep19-4LF通过与这种损伤相关的分子模式结合,阻止了人类单核细胞中硫酸乙酰肝素引起的肿瘤坏死因子α的释放。

此项研究表明:创伤相关的HS导致LL-37的释放。宿主防御/抗菌肽Pep19-4LF的合成可以减轻与HS相关的器官损伤/功能障碍。

原始出处:
Yamada N, Martin LB, et al. Novel Synthetic, Host-defense Peptide Protects Against Organ Injury/Dysfunction in a Rat Model of Severe Hemorrhagic Shock. Ann Surg. 2017 Mar 10. doi: 10.1097/SLA.0000000000002186. 

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    2017-03-25 wincls
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    2017-03-23 1def5ef1m18(暂无匿称)

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    0