The protective effect of exosomes derived from bolbostemma paniculatum on sepsis-induced acute lung injury

doi:10.11958/20260566

Abstract

Abstract:

Objective To investigate the protective effect and the related mechanisms of bolbostemma paniculatum-derived nanoparticles (BDNPs) on acute lung injury (ALI) induced by sepsis in mice. Methods BDNPs were extracted by ultracentrifugation, and their characteristics were detected by transmission electron microscopy and nanoparticle tracking analysis. A mouse model of ALI induced by cecal ligation and puncture (CLP) was established. Thirty mice were randomly divided into the sham operation group (Sham group), the model group (CLP group) and the BDNPs treatment group (BDNPs group), with 10 mice in each group. After 24 hours of modeling, lung tissue samples were collected for HE staining to detect pathological changes. q-PCR was used to detect the expression changes of inflammatory factors (TNF-α, IL-1β and IL-18 mRNA) in lung tissue. Transcriptome high-throughput sequencing was used to detect changes in signaling pathways in lung tissue. Western blot assay was used to detect the expression changes of pyroptosis-related proteins (NLRP3, GSDMD and Caspase-1) in lung tissue. 16S rDNA high-throughput sequencing was used to detect changes of intestinal flora. Results BDNP were successfully prepared by ultracentrifugation. Compared with the CLP group, BDNPs treatment could significantly improve the pathological damage of lung tissue and reduce the expression of TNF-α, IL-1β and IL-18 mRNA in lung tissue as well as the expression of NLRP3, GSDMD and Caspase-1 proteins in lung tissue (P<0.05). Compared with the Sham group, KEGG analysis indicated that the IL-17 signaling pathway and TNF-α signaling pathway and other inflammatory signaling pathway were enriched in the CLP group. Compared with the CLP group, BDNPs treatment could significantly reduce the related signaling pathways (P<0.05). BDNPs treatment could significantly improve the composition of intestinal flora, reduce the relative abundance of Acinetobacter and Shigella species, and significantly increase the relative abundance of Clostridium species (P<0.05). Conclusion BDNPs have a significant protective effect on CLP-induced ALI, and the mechanism may be related to improving the intestinal flora, inhibiting pyroptosis and reducing inflammatory responses.

Key words: bolbostemmatis rhizoma, exosomes, sepsis, acute lung injury, pyroptosis

CLC Number:

R631

Figures/Tables 8

References 23

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基因名称	引物序列（5′→3′）	产物大小/bp
GAPDH	上游：AGGTCGGTGTGAACGGATTTG 下游：GGGGTCGTTGATGGCAACA	202
TNF-α	上游：ATCTCTTCCCCACCCCGAAT 下游：GCGCCAAGCATTCAATGAGC	155
IL-1β	上游：GAAATGCCACCTTTTGACAGTG 下游：TGGATGCTCTCATCAGGACAG	116
IL-18	上游：GTGAACCCCAGACCAGACTG 下游：CCTGGAACACGTTTCTGAAAGA	202

基因名称	引物序列（5′→3′）	产物大小/bp
GAPDH	上游：AGGTCGGTGTGAACGGATTTG 下游：GGGGTCGTTGATGGCAACA	202
TNF-α	上游：ATCTCTTCCCCACCCCGAAT 下游：GCGCCAAGCATTCAATGAGC	155
IL-1β	上游：GAAATGCCACCTTTTGACAGTG 下游：TGGATGCTCTCATCAGGACAG	116
IL-18	上游：GTGAACCCCAGACCAGACTG 下游：CCTGGAACACGTTTCTGAAAGA	202

组别	TNF-α	IL-1β	IL-18
Sham组	1.00±0.03	1.03±0.25	1.02±0.20
CLP组	2.48±0.12^a	4.12±0.19^a	2.95±0.68^a
BDNPs组	1.46±0.05^b	1.91±0.30^b	1.49±0.19^b
F	169.000^＊＊	76.470^＊＊	11.210^＊＊

组别	TNF-α	IL-1β	IL-18
Sham组	1.00±0.03	1.03±0.25	1.02±0.20
CLP组	2.48±0.12^a	4.12±0.19^a	2.95±0.68^a
BDNPs组	1.46±0.05^b	1.91±0.30^b	1.49±0.19^b
F	169.000^＊＊	76.470^＊＊	11.210^＊＊

组别	NLRP3	GSDMD	Caspase-1
Sham组	0.36±0.06	0.43±0.01	0.29±0.01
CLP组	0.47±0.03^a	0.59±0.26^a	0.76±0.34^a
BDNPs组	0.34±0.04^b	0.45±0.07^b	0.31±0.19^b
F	6.078^＊	40.240^＊＊	100.300^＊＊