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人参皂苷 Rg1 通过 NF-κB/COX-2 信号通路保护后肢缺血再灌注诱导的肺损伤。

Ginsenoside Rg1 protects against hind-limb ischemia reperfusion induced lung injury via NF-κB/COX-2 signaling pathway.

机构信息

Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, People's Republic of China.

Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, People's Republic of China.

出版信息

Int Immunopharmacol. 2018 Jul;60:96-103. doi: 10.1016/j.intimp.2018.04.040. Epub 2018 Apr 27.

DOI:10.1016/j.intimp.2018.04.040
PMID:29709772
Abstract

BACKGROUND/AIMS: Ginsenoside Rg1 is regarded as the primary bioactive ingredient in Panax notoginseng that has been well recognized for its protective effects against ischemia/reperfusion (IR) injury. However, the mechanisms still remain elusive. Our study aims to investigate the effects of Rg1 against lung injury induced by hind-limb IR in rats.

METHODS

Twenty-four Sprague Dawley rats were randomly submitted to sham operation (SM group), hind-limb IR (IR group), hind-limb IR + Rg1 (Rg1 group), and hind-limb IR + Pro-DTC group (PD group). All the rats except those in SM group were subjected to 3 h of ischemia followed by 6 h of reperfusion, and extra intravenous Rg1 and pyrrolidine dithiocarbamate (Pro-DTC), a selective inhibitor of nuclear factor kappa B (NF-κB), was administered intravenously before ischemia in the Rg1 and PD group, respectively. The activities of myeloperoxidase (MPO), superoxide dismutase (SOD) and catalase (CAT), as well as protein expressions of NF-κB p65 and cyclooxygenases-2 (COX-2) in lung tissue, and thromboxane B2 (TXB2) and 6-keto-ProstaglandinF (6-keto-PGF) levels in bronchoalveolar lavage (BAL) fluid were detected. Morphological changes, index of quantitative assessment of histologic lung injury (IQA), apoptosis index (AI) and lung Wet/Dry ratio were also evaluated.

RESULTS

The levels of Wet/Dry ratio, IQA, AI, activities of MPO and 6-keto-PGF/TXB ratio were increased, and NF-κB p65 and COX-2 protein expression were upregulated, while SOD and CAT levels were decreased in lung tissue in IR group as compared with SM group (p < 0.05), all the alterations could be significantly reversed by Rg1 or Pro-DTC pretreatment (p < 0.05). And Rg1 and Pro-DTC also significantly attenuated the pulmonary histological abnormalities induced by IR.

CONCLUSION

Ginsenoside Rg1 potentially attenuated lung injury induced by hind-limb IR by regulating NF-κB/COX-2 signaling pathway.

摘要

背景/目的:人参皂苷 Rg1 被认为是三七中的主要生物活性成分,已被广泛认可具有抗缺血/再灌注 (IR) 损伤的作用。然而,其机制仍不清楚。本研究旨在探讨 Rg1 对大鼠后肢 IR 引起的肺损伤的作用。

方法

24 只 Sprague Dawley 大鼠随机分为假手术 (SM) 组、后肢 IR (IR) 组、后肢 IR+Rg1 (Rg1) 组和后肢 IR+吡咯烷二硫代氨基甲酸盐 (Pro-DTC) (PD) 组。除 SM 组外,所有大鼠均接受 3 h 缺血,然后再灌注 6 h,在 IR 组和 PD 组中,分别在缺血前静脉内给予额外的 Rg1 和吡咯烷二硫代氨基甲酸盐(NF-κB 的选择性抑制剂)。检测肺组织髓过氧化物酶 (MPO)、超氧化物歧化酶 (SOD) 和过氧化氢酶 (CAT) 的活性,以及 NF-κB p65 和环氧化酶-2 (COX-2) 的蛋白表达,以及支气管肺泡灌洗液 (BAL) 中的血栓素 B2 (TXB2) 和 6-酮-前列腺素 F (6-keto-PGF) 水平。还评估了形态学变化、组织学肺损伤定量评估指数 (IQA)、凋亡指数 (AI) 和肺湿/干比。

结果

与 SM 组相比,IR 组肺组织的湿/干比、IQA、AI、MPO 活性和 6-酮-PGF/TXB 比值升高,NF-κB p65 和 COX-2 蛋白表达上调,SOD 和 CAT 水平降低(p<0.05),Rg1 或 Pro-DTC 预处理可显著逆转所有改变(p<0.05)。Rg1 和 Pro-DTC 还显著减轻了 IR 引起的肺组织学异常。

结论

人参皂苷 Rg1 通过调节 NF-κB/COX-2 信号通路,可能减轻后肢 IR 引起的肺损伤。

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