精准医学杂志 (Dec 2023)
CHANGE IN INTESTINAL FLORA AND ITS ASSOCIATION WITH LIVER CYP2E1 IN MICE WITH LIVER INJURY INDUCED BY HIGH-INTENSITY ATORVASTATIN
Abstract
Objective To investigate the change in intestinal flora and its association with liver CYP2E1 in mice with li-ver injury caused by high-intensity atorvastatin (ATO). Methods According to the treatment method, 40 C57BL/6 mice were divided into low-intensity ATO group (ATO-L group), medium-intensity ATO group (ATO-M group), high-intensity ATO group (ATO-H group), and control group (CON group), with 10 rats in each group. The mice in the ATO-L group, the ATO-M group, and the ATO-H group were given 1 mL normal saline containing ATO at doses of 10, 20, and 30 mg/kg, respectively, by gavage, and those in the CON group were given an equal volume of normal saline by gavage, for 4 consecutive weeks. HE staining and transmission electron microscopy were used to observe liver pathological state. Related methods were used to measure the se-rum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10, the activity of superoxide dismutase (SOD) in liver tissue, and the mRNA expression level of CYP2E1 in liver tissue. 16SrDNA sequencing was used to analyze the distribution of intestinal flora in fresh feces of mice, and a correlation analysis was conducted to investigate the correlation of the relative abundance of bacterial genera with significant diffe-rences with the mRNA expression level of CYP2E1 and SOD activity in liver tissue. Results HE staining and transmission electron microscopy showed varying degrees of liver injury in the ATO-M and ATO-H groups. There were significant differences in the serum levels of ALT, AST, IL-6, and TNF-α and SOD activity in liver tissue between groups (F=4.57-7.74,P<0.05). Intestinal flora dysregulation was observed in the ATO-H group, and at the phylum level, there were significant differences in the relative abundance of Bacteroidetes, Firmicutes, Proteobacteria, and Deferribacteres between the ATO-H group and the CON group (t=2.89-5.22,P<0.05); at the family level, there were significant differences between these two groups in the relative abundance of Porphyromonadaceae, Prevotellaceae, Lactobacillaceae, Lachnospiraceae, and Helicobacteraceae (t=2.45-5.46,P<0.05). at the genus level, there were significant differences between these two groups in the relative abundance of Helicobacter, Alloprevotella, Prevotella, and Lactobacillus (t=2.46-7.41,P<0.05). The relative abundance of Lactobacillus was positively correlated with SOD activity in liver tissue (r=0.48,P<0.05) and was negatively correlated with the mRNA expression level of CYP2E1 in liver tissue (r=-0.62,P<0.05). Conclusion High-intensity statins may induce intestinal flora dysregulation and reduce anti-oxidative stress ability in mice, and the reduction in Lactobacillus may promote oxidative stress response of the liver.
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