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Neuropeptide W Attenuates Oxidative Multi-Organ Injury in Rats Induced with Intra-Abdominal Sepsis
Inflammation ( IF 5.1 ) Pub Date : 2021-09-25 , DOI: 10.1007/s10753-021-01545-5
Ali Emre Atici 1 , Sevil Arabacı Tamer 2 , Hilal Nişva Levent 3 , İrem Peker Eyüboğlu 4 , Feriha Ercan 3 , Mustafa Akkiprik 4 , Berrak Ç Yeğen 2
Affiliation  

Sepsis leads to systemic hypotension, disturbed perfusion, inflammation, and tissue toxicity in vital organs. Neuropeptide W (NPW) has modulatory effects in the control of blood pressure and inflammatory processes, implicating a potential beneficial effect against sepsis-induced oxidative damage. Under anesthesia, male Sprague Dawley rats underwent cecal ligation and puncture. Immediately after surgery, either saline or TNF-alpha inhibitor (etanercept; 1 mg/kg) antibiotic (ceftriaxon; 10 mg/kg) combination or NPW (0.1, 1, or 3 μg/kg) was given subcutaneously, and injections were repeated on the 12th and 24th h. The sham-operated control group was treated with saline at the same time points. All rats were euthanized on the 25th h of surgery. Sepsis resulted in oxidative damage of the brain, heart, lung, liver, and kidney. Elevations in blood urea nitrogen and alkaline phosphatase, showing renal and hepatic dysfunction, were not evident when septic rats were treated with NPW. NPW reduced serum levels of C-reactive protein, corticosterone, and interleukin-6, while histopathologically verified tissue damage in all the studied tissues was ameliorated. NPW treatment suppressed lipid peroxidation in the heart, lung, and brain, and the depleted antioxidant GSH levels of the brain and heart were replenished by NPW. Moreover, sepsis-related neutrophil recruitment to the liver and lung was also suppressed by NPW. Although the survival rate of the rats was not significantly prolonged by NPW, most of these improvements in systemic and local inflammatory events were comparable with those reached by the etanercept and antibiotic combination, suggesting the therapeutic impact of NPW during the acute period of sepsis.



中文翻译:

神经肽 W 减轻腹腔内脓毒症所致大鼠的氧化性多器官损伤

脓毒症导致全身性低血压、灌注障碍、炎症和重要器官的组织毒性。神经肽 W (NPW) 在控制血压和炎症过程中具有调节作用,暗示对脓毒症诱导的氧化损伤具有潜在的有益作用。在麻醉下,雄性 Sprague Dawley 大鼠进行盲肠结扎和穿刺。手术后立即皮下给予生理盐水或 TNF-α 抑制剂(依那西普;1 mg/kg)抗生素(头孢曲松;10 mg/kg)组合或 NPW(0.1、1 或 3 μg/kg),并重复注射在 12 日和 24 日。假手术对照组在同一时间点给予生理盐水治疗。所有大鼠在手术后第 25 小时处以安乐死。败血症导致脑、心脏、肺、肝和肾的氧化损伤。用 NPW 治疗脓毒症大鼠时,血液尿素氮和碱性磷酸酶的升高(显示肾和肝功能障碍)并不明显。NPW 降低了 C 反应蛋白、皮质酮和白细胞介素 6 的血清水平,同时改善了所有研究组织中的组织病理学证实的组织损伤。NPW 治疗抑制了心脏、肺和大脑中的脂质过氧化,并且大脑和心脏中耗尽的抗氧化剂 GSH 水平被 NPW 补充。此外,与脓毒症相关的中性粒细胞向肝脏和肺的募集也被 NPW 抑制。尽管 NPW 并未显着延长大鼠的存活率,但大多数全身和局部炎症事件的改善与依那西普和抗生素组合所达到的改善相当,

更新日期:2021-09-25
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