[Effect of mogroside VI on acute liver injury induced by sepsis in mice and related mechanisms].
Zhongguo Dang Dai Er Ke Za Zhi
; 22(11): 1233-1239, 2020 Nov.
Article
en Zh
| MEDLINE
| ID: mdl-33172561
ABSTRACT
OBJECTIVE:
To study the effect of mogroside VI (MVI) on acute liver injury induced by sepsis in mice and its possible mechanisms. Methods A total of 60 male C57BL/6 mice were randomly divided into five groups sham-operation, model, low-dose MVI (25 mg/kg), high-dose MVI (100 mg/kg), peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) inhibitor (100 mg/kg MVI+30 mg/kg PGC-1α inhibitor SR-18292), with 12 mice in each group. Cecal ligation and puncture were performed to establish a mouse model of sepsis. The drugs were given by intraperitoneal injection after the model was established, once a day for 3 consecutive days. ELISA was used to measure the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Colorimetry was used to measure the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in liver tissue. Hematoxylin-eosin staining was used to observe liver histopathological changes. Liver mitochondrial respiratory function was measured, and mitochondrial respiratory control rate was calculated. RT-PCR was used to measure the copy number of mitochondrial DNA (mtDNA) in liver tissue and the mRNA expression levels of PGC-1α, nuclear respiratory factor-1 (NRF-1), and mitochondrial transcription factor A (TFAM) in liver tissue. Western blot was used to measure the protein expression levels of PGC-1α, NRF-1, and TFAM in liver tissue.RESULTS:
Compared with the sham-operation group, the model group had significant increases in the serum levels of ALT and AST and the content of MDA in liver tissue (P<0.05) and significant reductions in the activities of GSH-Px and SOD in liver tissue (P<0.05). The model group had also severe liver histopathological injury and significant reductions in the mitochondrial respiratory control rate, the copy number of mtDNA, and the mRNA and protein expression levels of PGC-1α, NRF-1, and TFAM in liver tissue (P<0.05). Compared with the model group, the high-dose group had significant reductions in the serum levels of ALT and AST and the content of MDA in liver tissue (P<0.05), significant increases in the activities of GSH-Px and SOD in liver tissue (P<0.05), significant improvement in liver histopathological injury, and significant increases in the mitochondrial respiratory control rate, the copy number of mtDNA, and the mRNA and protein expression levels of PGC-1α, NRF-1, and TFAM in liver tissue (P<0.05). There were no significant differences in the above indicators between the low-dose and model groups (P>0.05). The PGC-1α inhibitor SR-18292 significantly inhibited the intervention effect of high-dose MVI (P<0.05).CONCLUSIONS:
MVI can effectively alleviate acute liver injury caused by sepsis in mice, possibly by enhancing mitochondrial biosynthesis mediated by PGC-1α.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Triterpenos
/
Sepsis
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
Zh
Revista:
Zhongguo Dang Dai Er Ke Za Zhi
Año:
2020
Tipo del documento:
Article
País de afiliación:
China