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甘草酸治疗通过抑制环氧化酶-2 和诱导型一氧化氮合酶表达,减轻脂多糖诱导的急性肺损伤。

Glycyrrhizin treatment is associated with attenuation of lipopolysaccharide-induced acute lung injury by inhibiting cyclooxygenase-2 and inducible nitric oxide synthase expression.

机构信息

Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.

出版信息

J Surg Res. 2011 Jan;165(1):e29-35. doi: 10.1016/j.jss.2010.10.004. Epub 2010 Nov 10.

Abstract

Glycyrrhizin (GL), a major active constituent of licorice root, has been attributed numerous pharmacologic effects, including anti-inflammatory, anti-viral, anti-tumor, and hepatoprotective activities. In this study, we investigated the anti-inflammatory effect of GL on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. ALI was induced in Balb/c mice by intratracheal instillation of LPS (1 mg/kg). Before 1 h of LPS administration, the mice received intraperitoneal injection of GL at varied doses (10, 25, and 50 mg/kg). The severity of pulmonary injury was evaluated 12 h after LPS administration. GL pretreatment led to significant attenuation of LPS induced evident lung histopathologic changes, alveolar hemorrhage, and neutrophil infiltration with evidence of reduced myeloperoxidase (MPO) activity. The lung wet/dry weight ratios, as an index of lung edema, were markedly reduced by GL pretreatment. The concentrations of pro-inflammatory cytokines interleukin (IL)-1β and tumor necrosis factor (TNF)-α were elevated in bronchoalveolar lavage fluid (BALF) after LPS administration, which were significantly inhibited by GL pretreatment. GL pretreatment also reduced the concentrations of nitric oxide (NO) in lung tissues. Furthermore, the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) was suppressed by GL pretreatment. In conclusion, GL potently protected against LPS-induced ALI, and the protective effects of GL may attribute partly to the suppression of COX-2 and iNOS expression.

摘要

甘草酸(GL)是甘草根的主要活性成分之一,具有多种药理作用,包括抗炎、抗病毒、抗肿瘤和保肝作用。在本研究中,我们研究了 GL 对脂多糖(LPS)诱导的小鼠急性肺损伤(ALI)的抗炎作用。通过气管内滴注 LPS(1mg/kg)在 Balb/c 小鼠中诱导 ALI。在 LPS 给药前 1 小时,小鼠接受不同剂量(10、25 和 50mg/kg)的腹腔注射 GL。在 LPS 给药后 12 小时评估肺损伤的严重程度。GL 预处理导致 LPS 诱导的明显肺组织病理变化、肺泡出血和中性粒细胞浸润明显减轻,髓过氧化物酶(MPO)活性降低。GL 预处理还明显降低了肺湿/干重比,作为肺水肿的指标。LPS 给药后支气管肺泡灌洗液(BALF)中促炎细胞因子白细胞介素(IL)-1β和肿瘤坏死因子(TNF)-α的浓度升高,GL 预处理显著抑制了这些浓度的升高。GL 预处理还降低了肺组织中一氧化氮(NO)的浓度。此外,GL 预处理抑制了环氧化酶-2(COX-2)和诱导型一氧化氮合酶(iNOS)的表达。总之,GL 能有效对抗 LPS 诱导的 ALI,GL 的保护作用可能部分归因于抑制 COX-2 和 iNOS 的表达。

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