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急性胰腺炎发作后己酮可可碱是否存在治疗窗?

Is there a therapeutic window for pentoxifylline after the onset of acute pancreatitis?

作者信息

Coelho Ana Maria Mendonça, Kunitake Tiago Alexandre, Machado Marcel Cerqueira Cesar, Martins Joilson Oliveira, Patzina Rosely Antunes, D'Albuquerque Luiz Augusto Carneiro, Jukemura José

机构信息

Laboratory of Liver Transplantation and Experimental Surgery, Department of Gastroenterology, Medical School, University of São Paulo, Brazil.

出版信息

Acta Cir Bras. 2012 Jul;27(7):487-93. doi: 10.1590/s0102-86502012000700010.

Abstract

PURPOSE

To investigate the effects of pentoxifylline (PTX) in experimental acute pancreatitis (AP) starting drug administration after the induction of the disease.

METHODS

One hundred male Wistar rats were submitted to taurocholate-induced AP and divided into three groups: Group Sham: sham-operated rats, Group Saline: AP plus saline solution, and Group PTX: AP plus PTX. Saline solution and PTX were administered 1 hour after induction of AP. At 3 hours after AP induction, peritoneal levels of tumor necrosis factor (TNF)-α, and serum levels of interleukin (IL)-6 and IL-10 levels were assayed by Enzyme-Linked Immunosorbent Assay (ELISA). Determinations of lung myeloperoxidase activity (MPO), histological analysis of lung and pancreas, and mortality study were performed.

RESULTS

PTX administration 1 hour after induction of AP caused a significant decrease in peritoneal levels of TNF-α and in serum levels of IL-6 and IL-10 when compared to the saline group. There were no differences in lung MPO activity between the two groups with AP. A decrease in mortality was observed in the PTX treatment compared to the saline group.

CONCLUSIONS

Administration of PTX after the onset of AP decreased the systemic levels of proinflammatory cytokines, raising the possibility that there is an early therapeutic window for PTX after the initiation of AP.

摘要

目的

研究己酮可可碱(PTX)在疾病诱导后开始给药对实验性急性胰腺炎(AP)的影响。

方法

将100只雄性Wistar大鼠诱导产生牛磺胆酸盐诱导的AP,并分为三组:假手术组:假手术大鼠;生理盐水组:AP加生理盐水溶液;PTX组:AP加PTX。在诱导AP后1小时给予生理盐水溶液和PTX。在诱导AP后3小时,通过酶联免疫吸附测定(ELISA)检测腹腔内肿瘤坏死因子(TNF)-α水平以及血清白细胞介素(IL)-6和IL-10水平。进行肺髓过氧化物酶活性(MPO)测定、肺和胰腺组织学分析以及死亡率研究。

结果

与生理盐水组相比,诱导AP后1小时给予PTX导致腹腔内TNF-α水平以及血清IL-6和IL-10水平显著降低。两组患AP的大鼠肺MPO活性无差异。与生理盐水组相比,PTX治疗组死亡率降低。

结论

AP发作后给予PTX可降低促炎细胞因子的全身水平,提示AP发病后PTX可能存在早期治疗窗。

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