一种模拟促红细胞生成素 3D 结构的非促红细胞生成肽可减少实验性失血性休克中的器官损伤/功能障碍和炎症。,Molecular Medicine

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一种模拟促红细胞生成素 3D 结构的非促红细胞生成肽可减少实验性失血性休克中的器官损伤/功能障碍和炎症。
Molecular Medicine ( IF 6.0 ) Pub Date : 2011-05-13 , DOI: 10.2119/molmed.2011.00053
Nimesh S A Patel ₁ , Kiran K Nandra , Michael Brines , Massimo Collino , Ws Fred Wong , Amar Kapoor , Elisa Benetti , Fera Y Goh , Roberto Fantozzi , Anthony Cerami , Christoph Thiemermann

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最近的研究表明，红细胞生成素对红细胞的分化和存活至关重要，在包括肾脏和肺在内的多种组织中具有细胞保护作用。然而，促红细胞生成素已被证明具有严重的副作用——增加血栓血管效应。我们研究了焦谷氨酸螺旋 B 表面肽 (pHBSP)，一种模拟促红细胞生成素 3D 结构的非促红细胞生成组织保护肽，是否可以防止遭受严重失血性休克 (HS) 的大鼠的器官损伤/功能障碍和炎症。平均动脉血压降低至 35 ± 5 mmHg 持续 90 分钟，然后用 20 mL/kg 乳酸林格酸盐复苏 10 分钟和 50% 的流血 50 分钟。复苏开始后 4 小时对大鼠实施安乐死。在复苏后 30 分钟或 60 分钟给予 pHBSP。HS 导致显着的器官损伤/功能障碍（肾、肝、胰腺、神经肌肉、肺）和炎症（肺）。在接受 HS 的大鼠中，pHBSP 显着减轻 (i) 器官损伤/功能障碍（肾、肝、胰腺、神经肌肉、肺）和炎症（肺），(ii) 增加 Akt、糖原合酶激酶-3β 和内皮硝酸的磷酸化氧化合酶，(iii) 减弱核因子 (NF)-κB 的激活和 (iv) 减弱 p38 和细胞外信号调节激酶 (ERK)1/2 磷酸化的增加。pHBSP 通过可能涉及激活 Akt 和内皮一氧化氮合酶的机制，防止严重失血性休克引起的多器官损伤/功能障碍和炎症，

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A nonerythropoietic peptide that mimics the 3D structure of erythropoietin reduces organ injury/dysfunction and inflammation in experimental hemorrhagic shock.

Recent studies have shown that erythropoietin, critical for the differentiation and survival of erythrocytes, has cytoprotective effects in a wide variety of tissues, including the kidney and lung. However, erythropoietin has been shown to have a serious side effect-an increase in thrombovascular effects. We investigated whether pyroglutamate helix B-surface peptide (pHBSP), a nonerythropoietic tissue-protective peptide mimicking the 3D structure of erythropoietin, protects against the organ injury/ dysfunction and inflammation in rats subjected to severe hemorrhagic shock (HS). Mean arterial blood pressure was reduced to 35 ± 5 mmHg for 90 min followed by resuscitation with 20 mL/kg Ringer Lactate for 10 min and 50% of the shed blood for 50 min. Rats were euthanized 4 h after the onset of resuscitation. pHBSP was administered 30 min or 60 min into resuscitation. HS resulted in significant organ injury/dysfunction (renal, hepatic, pancreas, neuromuscular, lung) and inflammation (lung). In rats subjected to HS, pHBSP significantly attenuated (i) organ injury/dysfunction (renal, hepatic, pancreas, neuromuscular, lung) and inflammation (lung), (ii) increased the phosphorylation of Akt, glycogen synthase kinase-3β and endothelial nitric oxide synthase, (iii) attenuated the activation of nuclear factor (NF)-κB and (iv) attenuated the increase in p38 and extracellular signal-regulated kinase (ERK)1/2 phosphorylation. pHBSP protects against multiple organ injury/dysfunction and inflammation caused by severe hemorrhagic shock by a mechanism that may involve activation of Akt and endothelial nitric oxide synthase, and inhibition of glycogen synthase kinase-3β and NF-κB.

更新日期：2019-11-01

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