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甜菊苷可保护 LPS 诱导的小鼠急性肺损伤。

Stevioside protects LPS-induced acute lung injury in mice.

机构信息

Department of Rheumatology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, Heilongjiang Province, 150086, People's Republic of China.

出版信息

Inflammation. 2013 Feb;36(1):242-50. doi: 10.1007/s10753-012-9540-8.

Abstract

Stevioside, a diterpene glycoside component of Stevia rebaudiana, has been known to exhibit anti-inflammatory properties. To evaluate the effect and the possible mechanism of stevioside in lipopolysaccharide (LPS)-induced acute lung injury, male BALB/c mice were pretreated with stevioside or dexamethasone 1 h before intranasal instillation of LPS. Seven hours later, tumor necrosis factor-α, interleukin-1β, and interleukin-6 in bronchoalveolar lavage fluid (BALF) were measured by using enzyme-linked immunosorbent assay. The number of total cells, neutrophils, and macrophages in the BALF were also determined. The right lung was excised for histological examination and analysis of myeloperoxidase activity and nitrate/nitrite content. Cyclooxygenase 2 (COX-2), inducible NO synthase (iNOS), nuclear factor-kappa B (NF-κB), inhibitory kappa B protein were detected by western blot. The results showed that stevioside markedly attenuated the LPS-induced histological alterations in the lung. Stevioside inhibited the production of pro-inflammatory cytokines and the expression of COX-2 and iNOS induced by LPS. In addition, not only was the wet-to-dry weight ratio of lung tissue significantly decreased, the number of total cells, neutrophils, and macrophages in the BALF were also significantly reduced after treatment with stevioside. Moreover, western blotting showed that stevioside inhibited the phosphorylation of IκB-α and NF-κB caused by LPS. Taken together, our results suggest that anti-inflammatory effect of stevioside against the LPS-induced acute lung injury may be due to its ability of inhibition of the NF-κB signaling pathway. Stevioside may be a promising potential therapeutic reagent for acute lung injury treatment.

摘要

甜菊苷是甜叶菊的二萜糖苷成分,具有抗炎特性。为了评估甜菊苷对脂多糖(LPS)诱导的急性肺损伤的作用和可能的机制,雄性 BALB/c 小鼠在鼻内滴注 LPS 前 1 小时用甜菊苷或地塞米松预处理。7 小时后,通过酶联免疫吸附试验测定支气管肺泡灌洗液(BALF)中肿瘤坏死因子-α、白细胞介素-1β和白细胞介素-6的含量。还测定了 BALF 中总细胞、中性粒细胞和巨噬细胞的数量。切除右肺进行组织学检查和髓过氧化物酶活性及硝酸盐/亚硝酸盐含量分析。通过 Western blot 检测环氧化酶 2(COX-2)、诱导型一氧化氮合酶(iNOS)、核因子-κB(NF-κB)、抑制性κB 蛋白。结果表明,甜菊苷显著减轻了 LPS 诱导的肺组织学改变。甜菊苷抑制了 LPS 诱导的促炎细胞因子的产生和 COX-2 和 iNOS 的表达。此外,甜菊苷处理后肺组织的湿重/干重比显著降低,BALF 中总细胞、中性粒细胞和巨噬细胞的数量也显著减少。此外,Western blot 显示甜菊苷抑制了 LPS 引起的 IκB-α 和 NF-κB 的磷酸化。综上所述,我们的研究结果表明,甜菊苷对 LPS 诱导的急性肺损伤的抗炎作用可能与其抑制 NF-κB 信号通路的能力有关。甜菊苷可能是一种有前途的急性肺损伤治疗潜在治疗试剂。

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