Systematic identification of the interventional mechanism of Qingfei Xiaoyan Wan (QFXYW) in treatment of the cytokine storm in acute lung injury using transcriptomics-based system pharmacological analyses

基于转录组学的系统药理学分析系统鉴定清肺消炎丸治疗急性肺损伤细胞因子风暴的干预机制

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作者:Jing-Yi Hou, Jia-Rong Wu, Yi-Bing Chen, Dong Xu, Shu Liu, Dan-Dan Shang, Guan-Wei Fan, Yuan-Lu Cui

Conclusions

This study showed that QFXYW decreased the number of leukocytes and neutrophils by attenuating inflammatory response, which provides an important basis for the use of QFXYW in the treatment of ALI.

Methods

BALB/c Mice in each group were first orally administered medicines (0.9% saline solution for the control group, 0.5 mg/kg Dexamethasone, or 1.3, 2.6, 5.2 g/kg QFXYW), after 4 h, the groups were injected LPS (1.0 mg/kg) to induce ALI, then the same medicines were administered repeatedly. The transcriptomics-based system pharmacological analyses were applied to screen the hub genes, RT-PCR, ELISA, and protein array assay was applied to verify the predicted hub genes and key pathways.

Objective

This study evaluates the potential effects and elucidates the therapeutic mechanism of QFXYW against LPS induced ALI in mice. Materials and

Results

QFXYW significantly decreased the number of leukocytes from (6.34 ± 0.51) × 105/mL to (4.01 ± 0.11) × 105/mL, accompanied by the neutrophil from (1.41 ± 0.19) × 105/mL to (0.77 ± 0.10) × 105/mL in bronchoalveolar lavage fluid (BALF). Based on Degree of node connection (Degree) and BottleNeck (BN), important parameters of network topology, the protein-protein interaction (PPI) network screened hub genes, including IL-6, TNF-α, CCL2, TLR2, CXCL1, and MMP-9. The results of RT-PCR, ELISA, and protein chip assay revealed that QFXYW could effectively inhibit ALI via multiple key targets and the cytokine-cytokine signalling pathway. Conclusions: This study showed that QFXYW decreased the number of leukocytes and neutrophils by attenuating inflammatory response, which provides an important basis for the use of QFXYW in the treatment of ALI.

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