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17-羟基乔松素内酯B衍生物HJB-1对脂多糖诱导的急性呼吸窘迫综合征小鼠的保护作用

The Protective Effects of HJB-1, a Derivative of 17-Hydroxy-Jolkinolide B, on LPS-Induced Acute Distress Respiratory Syndrome Mice.

作者信息

Xu Xiaohan, Liu Ning, Zhang Yu-Xin, Cao Jinjin, Wu Donglin, Peng Qisheng, Wang Hong-Bing, Sun Wan-Chun

机构信息

Central Laboratory, The Second Clinical Hospital, Jilin University, Changchun 130041, China.

Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun 130062, China.

出版信息

Molecules. 2016 Jan 11;21(1):77. doi: 10.3390/molecules21010077.

Abstract

Acute respiratory distress syndrome (ARDS),which is inflammatory disorder of the lung, which is caused by pneumonia, aspiration of gastric contents, trauma and sepsis, results in widespread lung inflammation and increased pulmonary vascular permeability. Its pathogenesis is complicated and the mortality is high. Thus, there is a tremendous need for new therapies. We have reported that HJB-1, a 17-hydroxy-jolkinolide B derivative, exhibited strong anti-inflammatory effects in vitro. In this study, we investigated its impacts on LPS-induced ARDS mice. We found that HJB-1 significantly alleviated LPS-induced pulmonary histological alterations, inflammatory cells infiltration, lung edema, as well as the generation of inflammatory cytokines TNF-α, IL-1β and IL-6 in BALF. In addition, HJB-1 markedly suppressed LPS-induced IκB-α degradation, nuclear accumulation of NF-κB p65 subunit and MAPK phosphorylation. These results suggested that HJB-1 improved LPS-induced ARDS by suppressing LPS-induced NF-κB and MAPK activation.

摘要

急性呼吸窘迫综合征(ARDS)是一种肺部炎症性疾病,由肺炎、胃内容物误吸、创伤和脓毒症引起,可导致广泛的肺部炎症和肺血管通透性增加。其发病机制复杂,死亡率高。因此,迫切需要新的治疗方法。我们曾报道,HJB-1(一种17-羟基jolkinolide B衍生物)在体外具有强大的抗炎作用。在本研究中,我们研究了其对脂多糖(LPS)诱导的ARDS小鼠的影响。我们发现,HJB-1显著减轻了LPS诱导的肺部组织学改变、炎性细胞浸润、肺水肿以及支气管肺泡灌洗液(BALF)中炎性细胞因子肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)的产生。此外,HJB-1明显抑制了LPS诱导的IκB-α降解、核因子κB(NF-κB)p65亚基的核内积聚以及丝裂原活化蛋白激酶(MAPK)磷酸化。这些结果表明,HJB-1通过抑制LPS诱导的NF-κB和MAPK活化来改善LPS诱导的ARDS。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dcd/6273719/e8793be3dfa7/molecules-21-00077-g001.jpg

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