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穿心莲内酯磺酸盐通过下调丝裂原活化蛋白激酶(MAPK)和核因子κB(NF-κB)信号通路减轻脂多糖诱导的小鼠急性肺损伤。

Andrographolide sulfonate ameliorates lipopolysaccharide-induced acute lung injury in mice by down-regulating MAPK and NF-κB pathways.

作者信息

Peng Shuang, Hang Nan, Liu Wen, Guo Wenjie, Jiang Chunhong, Yang Xiaoling, Xu Qiang, Sun Yang

机构信息

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.

Jiangxi Qingfeng Pharmaceutical Co., Ltd., Ganzhou 341000, China; State Key Laboratory of Innovative Nature Medicine and TCM Injections, Jiangxi Qingfeng Pharmaceutical Co., Ltd., Ganzhou, 341000, China.

出版信息

Acta Pharm Sin B. 2016 May;6(3):205-11. doi: 10.1016/j.apsb.2016.02.002. Epub 2016 Mar 22.

Abstract

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a severe, life-threatening medical condition characterized by widespread inflammation in the lungs, and is a significant source of morbidity and mortality in the patient population. New therapies for the treatment of ALI are desperately needed. In the present study, we examined the effect of andrographolide sulfonate, a water-soluble form of andrographolide (trade name: Xi-Yan-Ping Injection), on lipopolysaccharide (LPS)-induced ALI and inflammation. Andrographolide sulfonate was administered by intraperitoneal injection to mice with LPS-induced ALI. LPS-induced airway inflammatory cell recruitment and lung histological alterations were significantly ameliorated by andrographolide sulfonate. Protein levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and serum were reduced by andrographolide sulfonate administration. mRNA levels of pro-inflammatory cytokines in lung tissue were also suppressed. Moreover, andrographolide sulfonate markedly suppressed the activation of mitogen-activated protein kinase (MAPK) as well as p65 subunit of nuclear factor-κB (NF-κB). In summary, these results suggest that andrographolide sulfonate ameliorated LPS-induced ALI in mice by inhibiting NF-κB and MAPK-mediated inflammatory responses. Our study shows that water-soluble andrographolide sulfonate may represent a new therapeutic approach for treating inflammatory lung disorders.

摘要

急性肺损伤(ALI)或急性呼吸窘迫综合征(ARDS)是一种严重的、危及生命的医学病症,其特征为肺部广泛炎症,是患者群体发病和死亡的重要原因。迫切需要治疗ALI的新疗法。在本研究中,我们检测了穿心莲内酯磺化物(穿心莲内酯的水溶性形式,商品名:喜炎平注射液)对脂多糖(LPS)诱导的ALI及炎症的影响。将穿心莲内酯磺化物腹腔注射给予LPS诱导的ALI小鼠。穿心莲内酯磺化物显著改善了LPS诱导的气道炎性细胞募集及肺组织学改变。给予穿心莲内酯磺化物后,支气管肺泡灌洗液(BALF)和血清中促炎细胞因子的蛋白水平降低。肺组织中促炎细胞因子的mRNA水平也受到抑制。此外,穿心莲内酯磺化物显著抑制丝裂原活化蛋白激酶(MAPK)以及核因子-κB(NF-κB)的p65亚基的激活。总之,这些结果表明穿心莲内酯磺化物通过抑制NF-κB和MAPK介导的炎症反应改善了LPS诱导的小鼠ALI。我们的研究表明水溶性穿心莲内酯磺化物可能代表一种治疗炎性肺部疾病的新治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52ec/4856950/a76186b95ac7/gr1.jpg

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