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Method of Direct Segmental Intra-hepatic Delivery Using a Rat Liver Hilar Clamp Model
Published on: April 2, 2017
SRT1720 Treatments Hepatic Ischemia Reperfusion Injury by Regulation of NF-κB Signaling Pathways and Reduce Cell
Zhongzhe Li1, Wenting Geng2, Beilei Yu1
1College of Sports Medicine and Rehabilitation, Shandong First Medical University &Shandong Academy Medical Sciences, 619 Changcheng Road, Taian 271016 Shandong, PR China.
Background And Objective:
Hepatic ischemia reperfusion injury (HIRI) is a common complication closely related to the prognosis of liver surgery, and effective treatment methods are still unavailable. SRT1720 has the characteristics of multifunction and multitarget which may cope with the multidirectional complex pathological process caused by HIRI. The present study aimed to explore the potential mechanism of SRT1720 in HIRI through a combination of network pharmacology, in vitro experiments and in vivo models.
Methods:
Differentially expressed genes (DEGs) were identified based on the GSE15480 and Genecards database. Enrichment analyses were then conducted. SRT1720-targeted genes were obtained through databases such as Chembl, TTD, GtoPdb, and so on. All target genes were standardized by the Uniprot database and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were identified by STRING. Shared KEGG pathways were identified using a Venn diagram among SRT1720-targeted pathways and HIRI. Furthermore, experimental techniques such as cell apoptosis assay and western blotting were used to confirm the most significant biological processes and the key pathway between SRT1720-targeted and HIRI.
Results:
This study identified 118 HIRI-related DEGs, 69 shared KEGG pathways of SRT1720 and HIRI. In addition, the findings revealed that SRT1720 significantly reduced liver ischemiareperfusion (I/R) injury. NF-κB signaling pathway and the expression of promoting apoptosis factors such as Bax and Caspase3 were inhibited, while antiapoptotic protein Bcl-2 was promoted in the SRT1720 group compared with the I/R group.
Conclusion:
The findings indicate that SRT1720 may inhibit the development of HIRI by inhibiting the NF-κB signaling pathway and reducing cell apoptosis, acting as a treatment for HIRI.
