Department of Respiratory Medicine, First Affiliated Hospital of China Medical University, Shenyang, China.
J Cell Physiol. 2019 Apr;234(4):4597-4607. doi: 10.1002/jcp.27242. Epub 2018 Sep 10.
This study aimed to explore glycyrrhizin on acute lung injury (ALI) and how glycyrrhizin (GL) attenuated lipopolysaccharide (LPS)-induced ALI.
Bioinformatics analysis was performed to screen the expressed genes in LPS-induced ALI mice. The enrichment of functions and signaling pathways of deregulated genes were conducted. Combined with DIGSEE and STICH, the target gene for further investigation was chosen. To verify target gene in mice, we performed experiment in vivo. Forty mice were randomized into NC, LPS, LPS + S, and LPS + GL group. Mice in the LPS + GL group received glycyrrhizin l mg and mice in LPS + S received saline. Then, HE and Masson staining detected pathological changes of lung tissues; enzyme-linked immunosorbent assay analyzed bronchoalveolar lavage fluid concentrations of MIP-2, mice growth-related oncogene homologue (KC), IL-4, IL-6, GM-CSF, IFN-γ, and IgM; western blot analysis determined the expression of toll-like receptor (TLR) signaling and NF-κB pathway-related proteins.
Tlr2 which was not only upregulated but also closely related to glycyrrhizin. TLR2 was upregulated in following LPS induced in cells and TLR2 overexpression-activated TLR signaling pathway to promote ALI. After glycyrrhizin treatment, the expression of TLR2 was reduced. Furthermore, it was found out that the number of inflammatory cells, collagen deposition, MIP-2, KC, IL-4, IL-6, GM-CSF, and IFN-γ expression increased in ALI mice and glycyrrhizin mitigated it. Similarly, the expression of TLR signaling pathway and NF-κB pathway-related protein also increased.
Glycyrrhizin functioned as a suppressor in TLR signaling pathway to reduce LPS-induced ALI by inhibiting TLR2.
本研究旨在探讨甘草酸对急性肺损伤（ALI）的作用机制，以及甘草酸（GL）如何减轻脂多糖（LPS）诱导的 ALI。
采用生物信息学分析筛选 LPS 诱导的 ALI 小鼠差异表达基因。对差异表达基因进行功能和信号通路富集分析。结合 DIGSEE 和 STICH，选择进一步研究的靶基因。为了验证该靶基因在小鼠体内的作用，我们进行了体内实验。将 40 只小鼠随机分为 NC、LPS、LPS+S 和 LPS+GL 组。LPS+GL 组给予甘草酸 1mg，LPS+S 组给予生理盐水。然后，HE 和 Masson 染色检测肺组织的病理变化；酶联免疫吸附试验分析支气管肺泡灌洗液中 MIP-2、小鼠生长相关癌基因同源物（KC）、IL-4、IL-6、GM-CSF、IFN-γ 和 IgM 的浓度；Western blot 分析测定 TLR 信号和 NF-κB 通路相关蛋白的表达。
Tlr2 不仅上调，而且与甘草酸密切相关。TLR2 在 LPS 诱导的细胞中上调，并激活 TLR 信号通路促进 ALI。甘草酸处理后，TLR2 的表达减少。此外，发现 ALI 小鼠的炎症细胞数、胶原沉积、MIP-2、KC、IL-4、IL-6、GM-CSF 和 IFN-γ 表达增加，甘草酸减轻了这种情况。同样，TLR 信号通路和 NF-κB 通路相关蛋白的表达也增加。
甘草酸作为 TLR 信号通路的抑制剂，通过抑制 TLR2 发挥作用，减轻 LPS 诱导的 ALI。
