The active GLP-1 analogue liraglutide alleviates H9N2 influenza virus-induced acute lung injury in mice
The active GLP-1 analogue liraglutide alleviates H9N2 influenza virus-induced acute lung injury in mice
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DOI：
10.1016/j.micpath.2020.104645
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发表时间：
2021-01-01
影响因子：
3.8
通讯作者：
Qiao, Jian
中科院分区：
文献类型：
--
作者：
Bai, Yu;Lian, Pengjing;Qiao, Jian
流感病毒是世界范围内重要的发病率和死亡率的原因。急性肺损伤（Acute lung injury，ALI）/急性呼吸窘迫综合征（acute respiratory distress syndrome，ARDS）是流感病毒感染患者的主要死亡原因。近年来研究表明，胰高血糖素（GCG）基因编码的活性胰高血糖素样肽-1（GLP-1）具有抗炎作用。本研究的目的是确定活性GLP-1在H9 N2流感病毒诱导的小鼠ALI/ARDS中的潜在作用。首先，我们发现，GCG mRNA表达水平和GCG前体蛋白水平显着增加，但总GLP-1和活性GLP-1水平在H9 N2感染小鼠的肺中下降。接下来，使用活性GLP-1类似物利拉鲁肽治疗感染小鼠，并观察其对H9 N2病毒诱导的ALI的影响。利拉鲁肽给药改善了感染小鼠中观察到的体重下降、摄食量减少和死亡率。减轻肺损伤程度，包括降低肺指数、减少炎性细胞浸润和降低支气管肺泡灌洗液（BALF）中总蛋白水平。此外，利拉鲁肽不影响感染肺中的病毒滴度，但降低BALF中白细胞介素-1 β、白细胞介素-6和肿瘤坏死因子-α的水平。这些结果表明，利拉鲁肽缓解了小鼠中H9 N2病毒诱导的ALI，这很可能是由于促炎细胞因子水平较低。
Influenza virus is responsible for significant morbidity and mortality worldwide. Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is the major cause of death in influenza virus infected patients. Recent studies indicated that active glucagon like peptide-1 (GLP-1) encoded by glucagon (GCG) gene exerts anti-inflammatory functions. The aim of this study was to determine the potential role of active GLP-1 in H9N2 influenza virus-induced ALI/ARDS in mice. First, we uncovered that GCG mRNA expression levels and GCG precursor protein levels were significantly increased, but total GLP-1 and active GLP-1 levels were decreased in the lungs of H9N2-infected mice. Next, liraglutide, an active GLP-1 analogue, was used to treat infected mice and to observe its effects on H9N2 virus-induced ALI. Liraglutide treatment ameliorated the declined body weight, decreased food intake and mortality observed in infected mice. It also alleviated the severity of lung injury, including lowering lung index, decreasing inflammatory cell infiltration and lowing total protein levels in bronchoalveolar lavage fluid (BALF). In addition, liraglutide did not influence viral titers in infected lungs, but decreased the levels of interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha in BALF. These results indicated that liraglutide alleviated H9N2 virus-induced ALI in mice most likely due to lower levels of pro-inflammatory cytokines.