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评价 N-乙酰半胱氨酸在急性胰腺炎相关性肺损伤中的治疗作用。

Evaluation of N-acetylcysteine treatment in acute pancreatitis-induced lung injury.

机构信息

Departamento Fisiología y Farmacología-IBSAL, University of Salamanca, Edificio Departamental, Campus Miguel de Unamuno, 37007 Salamanca, Spain.

出版信息

Inflamm Res. 2012 Jul;61(7):699-705. doi: 10.1007/s00011-012-0462-6. Epub 2012 Mar 23.

Abstract

OBJECTIVE

Pulmonary complications are frequent during acute pancreatitis (AP). We investigate the effects of N-acetylcysteine (NAC) on lung injury in mild and severe AP. ANIMALS AND TREATMENT: Mild and severe AP was induced in rats by bile-pancreatic duct obstruction (BPDO) and infusion of 3.5 % sodium taurocholate (NaTc) into the bile-pancreatic duct, respectively. NAC (50 mg/kg) was given 1 h before and 1 h after AP.

METHODS

Amylase activity was measured in plasma. Lungs were harvested for mRNA expression analysis of monocyte chemoattractant protein-1 (MCP-1), cytokine-induced neutrophil chemoattractant (CINC), P-selectin and intercellular adhesion molecule-1 (ICAM-1), myeloperoxidase (MPO) activity and histological examination.

RESULTS

Hyperamylasemia was reduced by NAC in both AP models. NAC down-regulated MCP-1, CINC and P-selectin in BPDO- but not in NaTc-induced AP. Pulmonary insults did not vary in mild AP and were exacerbated in severe AP by NAC treatment. NAC reduced lung MPO activity in mild but not in severe AP.

CONCLUSIONS

Although NAC treatment down-regulated inflammatory mediators in lungs during AP it did not prevent leukocyte infiltration, which could be responsible for maintaining the lung injury. As a result, NAC aggravated the lung damage in severe AP and failed to exert beneficial effects in the mild disease model.

摘要

目的

急性胰腺炎(AP)常伴有肺部并发症。本研究旨在探讨 N-乙酰半胱氨酸(NAC)对轻症和重症 AP 肺损伤的影响。

动物和处理方法

通过胆胰管阻塞(BPDO)和向胆胰管内注入 3.5%牛磺胆酸钠(NaTc)分别诱导大鼠轻症和重症 AP,NAC(50mg/kg)在 AP 前 1 小时和后 1 小时给予。

方法

检测血浆中淀粉酶活性。采集肺组织,进行单核细胞趋化蛋白-1(MCP-1)、细胞因子诱导的中性粒细胞趋化因子(CINC)、P-选择素和细胞间黏附分子-1(ICAM-1)mRNA 表达分析、髓过氧化物酶(MPO)活性和组织学检查。

结果

NAC 降低了两种 AP 模型中的高淀粉酶血症。NAC 在 BPDO 诱导的 AP 中下调 MCP-1、CINC 和 P-选择素,但在 NaTc 诱导的 AP 中没有作用。轻症 AP 中肺损伤没有变化,NAC 治疗加重了重症 AP 中的肺损伤。NAC 降低了轻症 AP 中的肺 MPO 活性,但对重症 AP 没有作用。

结论

尽管 NAC 治疗在 AP 期间下调了肺部的炎症介质,但并未阻止白细胞浸润,这可能是导致肺损伤持续存在的原因。结果,NAC 在重症 AP 中加重了肺损伤,在轻症疾病模型中未能发挥有益作用。

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