Sirt1 involved in sepsis-induced acute liver injury <i>via</i> regulating HNF-1α/FXR-1 pathway: The mechanism study in a rodent model

Abstract

Abstract:

Objective:To investigate the role of Silent information regulator 1 (SIRT1) in sepsis-induced liver injury and the related mechanism in a mouse model.Methods:A mouse sepsis model was established by intraperitoneal injection (IP) of LPS, and the mice in control group were only given same volume sterilized 0.9% saline via IP. Sections of the liver from the mice in both groups were stained with hematoxylin-eosin and hepatic injury was examined, and quantitative real-time polymerase chain reaction (qrt-PCR) was performed to detect expression of Sirt1/HNF-1α/FXR-1 in hepatic tissue. The isolated primary mouse hepatic parenchymal cells were treated with different concentrations of LPS. Viabilityand proliferation of hepatic parenchymal cells were evaluated by CCK8 and EdU assay respectively. In addition, enzyme linked immunosorbent assay (ELISA) was conducted to measure interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) production in hepatic parenchymal cells treated with different concentration of LPS. Sirt1 overexpressing plasmids were constructed and transfected into hepatic cells in mediation of Lipofectamine 2000. After 48 hour, the Sirt1/HNF-1α/FXR-1 pathway expression was tested by qrt-PCR and the impact of overexpressing Sirt1 on the function of the cells was evaluated by CCK8, EdU and ELISA.Results:Compared with control, Sirt1/HNF-1α/FXR-1 pathway was down-regulated in LPS-induced sepsis mouse model. LPS lowered cell viability, inhibited proliferation and increased secretion of inflammatory factors IL-6 and TNF-α in hepatocytes. Over-expression of Sirt1 upregulated the expression of HNF-1α/FXR-1 pathway in parenchymal cells, alleviated LPS-induced inhibition of cell viability and proliferation, and decreased LPS-induced inflammatory factor secretion.Conclusions:The Sirt1/HNF-1α/FXR-1 pathway is involved in LPS-induced septic liver injury. Overexpression of Sirt1 is able to attenuate the toxic effects of LPS on parenchymal cells.

Key words:Sepsis,LPS,Silent information regulator 1 (SIRT1),HNF-1α/FXR-1 pathway

CLC Number:

R575.3

WANG Qiuyun, CHEN Ying, ZHAO Bing, SUN Silei, YANG Zhitao, MAO Enqiang, CHEN Erzhen. Sirt1 involved in sepsis-induced acute liver injuryviaregulating HNF-1α/FXR-1 pathway: The mechanism study in a rodent model[J]. Journal of Diagnostics Concepts & Practice, 2020, 19(03): 279-285.

Figures/Tables6

基因	引物序列
Sirtq1上游	5'-GATACGGAGAGGCCCGAATG-3'
Sirtq1下游	5'-AGTTCCCAATGCTGGTGGAG-3'
FXR-1上游	5'-TCCTTGTCCTCCTCGGAACA-3'
FXR-1下游	5'-TGGGGTTTCCTGAAGCCTTG-3'
HNF-1α上游	5'-GTACGGACAGTCTGCAACCA-3'
HNF-1α下游	5'-TACTTGGTGTAAGGCCGCAG-3'
GAPDH上游	5'-AGGTCGGTGTGAACGGATTTG-3'
GAPDH下游	5'-GGGGTCGTTGATGGCAACA-3'

References21

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Sirt1 involved in sepsis-induced acute liver injuryviaregulating HNF-1α/FXR-1 pathway: The mechanism study in a rodent model

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[1]	.[J]. Journal of Diagnostics Concepts & Practice, 2015, 14(04): 363-366.
[2]	.[J]. Journal of Diagnostics Concepts & Practice, 2010, 9(01): 58-62.
[3]	.[J]. Journal of Diagnostics Concepts & Practice, 2009, 8(05): 484-486.