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吡咯烷二硫代氨基甲酸盐对链脲佐菌素诱导糖尿病大鼠肺损伤的核因子 kappa B 抑制剂的保护作用。

Protective effect of the nuclear factor kappa B inhibitor pyrrolidine dithiocarbamate in lung injury in rats with streptozotocin-induced diabetes.

机构信息

Department of Anesthesiology and Intensive Care, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey.

出版信息

Respiration. 2010;79(5):402-10. doi: 10.1159/000264920. Epub 2009 Dec 7.

Abstract

BACKGROUND

Diabetes mellitus (DM) causes debilitating complications and, as a result, diabetics frequently require intensive care. Although lungs are not thought to be affected primarily by DM, an increasing number of studies indicate physiological and structural abnormalities in diabetic lungs.

OBJECTIVES

Pyrrolidine dithiocarbamate (PDTC) is a metal chelator and a potent inhibitor of NF-kappaB. Keeping in mind that NF-kappaB activation may be crucial in end-organ injury due to DM, we studied the role of PDTC on the inhibition of NF-kappaB activation and its effects on possible lung injury in rats with streptozotocin-induced DM.

METHODS

36 Sprague-Dawley rats were allocated into 4 groups: diabetes, diabetes + PDTC, control and control + PDTC. At the end of 10 weeks, rats were sacrificed and their lungs were taken for histopathological and immunohistochemical evaluation [for NF-kappaB (p65) and endothelial nitric oxide (eNOS) immunoreactivities]. Protein carbonyl content (PCC), superoxide dismutase (SOD) and reduced glutathione (GSH) activities were measured.

RESULTS

Histopathologically, basal membranes were thickened and there was intense inflammatory reaction in diabetic lungs. However, the PDTC group, in which there were poor positive expressions of eNOS and p65 activity compared to diabetes group, revealed fewer inflammatory changes. PCC levels in diabetic lungs were higher, but SOD and GSH activities were lower. However, measurements of these parameters in the PDTC group and controls gave similar results.

CONCLUSION

Lungs are exposed to changes induced by oxidative stress in diabetes through NF-kappaB activation and PDTC seems to be useful to prevent diabetic lung injury.

摘要

背景

糖尿病(DM)会导致衰弱性并发症,因此糖尿病患者经常需要重症监护。尽管人们认为肺部不会受到 DM 的主要影响,但越来越多的研究表明,糖尿病患者的肺部存在生理和结构异常。

目的

吡咯烷二硫代氨基甲酸盐(PDTC)是一种金属螯合剂和 NF-κB 的有效抑制剂。考虑到 NF-κB 的激活可能在 DM 导致的终末器官损伤中至关重要,我们研究了 PDTC 对 NF-κB 激活的抑制作用及其对链脲佐菌素诱导的 DM 大鼠可能的肺损伤的影响。

方法

将 36 只 Sprague-Dawley 大鼠分为 4 组:糖尿病组、糖尿病+PDTC 组、对照组和对照组+PDTC 组。在 10 周结束时,处死大鼠并取其肺组织进行组织病理学和免疫组织化学评价[用于 NF-κB(p65)和内皮型一氧化氮合酶(eNOS)免疫反应性]。测量蛋白羰基含量(PCC)、超氧化物歧化酶(SOD)和还原型谷胱甘肽(GSH)的活性。

结果

组织病理学上,糖尿病大鼠的基底膜增厚,炎症反应强烈。然而,与糖尿病组相比,PDTC 组的 eNOS 和 p65 活性表达较弱,炎症变化较少。糖尿病大鼠的 PCC 水平较高,但 SOD 和 GSH 活性较低。然而,PDTC 组和对照组的这些参数测量结果相似。

结论

通过 NF-κB 激活,肺部暴露于糖尿病引起的氧化应激变化中,而 PDTC 似乎可用于预防糖尿病性肺损伤。

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