CHANGE IN INTESTINAL FLORA AND ITS ASSOCIATION WITH LIVER CYP2E1 IN MICE WITH LIVER INJURY INDUCED BY HIGH-INTENSITY ATORVASTATIN

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 A...

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Main Author: SONG Bingxue, SONG Yuqing, LIU Xin, YU Haichu, XIN Hui, LIANG Hui
Format: Article
Language:zho
Published: Editorial Office of Journal of Precision Medicine 2023-12-01
Series:精准医学杂志
Subjects:
Online Access:https://jpmed.qdu.edu.cn/fileup/2096-529X/PDF/1701928426310-1484774633.pdf
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author SONG Bingxue, SONG Yuqing, LIU Xin, YU Haichu, XIN Hui, LIANG Hui
author_facet SONG Bingxue, SONG Yuqing, LIU Xin, YU Haichu, XIN Hui, LIANG Hui
author_sort SONG Bingxue, SONG Yuqing, LIU Xin, YU Haichu, XIN Hui, LIANG Hui
collection DOAJ
description 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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spelling doaj.art-2c9cdc7a98924659903f6a31c6bba77a2024-03-12T06:31:42ZzhoEditorial Office of Journal of Precision Medicine精准医学杂志2096-529X2023-12-0138649449810.13362/j.jpmed.202306006CHANGE IN INTESTINAL FLORA AND ITS ASSOCIATION WITH LIVER CYP2E1 IN MICE WITH LIVER INJURY INDUCED BY HIGH-INTENSITY ATORVASTATINSONG Bingxue, SONG Yuqing, LIU Xin, YU Haichu, XIN Hui, LIANG Hui01 Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao 266100, ChinaObjective 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.https://jpmed.qdu.edu.cn/fileup/2096-529X/PDF/1701928426310-1484774633.pdfgastrointestinal microbiome|atorvastatin|chemical and drug induced liver injury|cytochrome p-450 enzyme system|rna, messenger|superoxide dismutase|lactobacillus
spellingShingle SONG Bingxue, SONG Yuqing, LIU Xin, YU Haichu, XIN Hui, LIANG Hui
CHANGE IN INTESTINAL FLORA AND ITS ASSOCIATION WITH LIVER CYP2E1 IN MICE WITH LIVER INJURY INDUCED BY HIGH-INTENSITY ATORVASTATIN
精准医学杂志
gastrointestinal microbiome|atorvastatin|chemical and drug induced liver injury|cytochrome p-450 enzyme system|rna, messenger|superoxide dismutase|lactobacillus
title CHANGE IN INTESTINAL FLORA AND ITS ASSOCIATION WITH LIVER CYP2E1 IN MICE WITH LIVER INJURY INDUCED BY HIGH-INTENSITY ATORVASTATIN
title_full CHANGE IN INTESTINAL FLORA AND ITS ASSOCIATION WITH LIVER CYP2E1 IN MICE WITH LIVER INJURY INDUCED BY HIGH-INTENSITY ATORVASTATIN
title_fullStr CHANGE IN INTESTINAL FLORA AND ITS ASSOCIATION WITH LIVER CYP2E1 IN MICE WITH LIVER INJURY INDUCED BY HIGH-INTENSITY ATORVASTATIN
title_full_unstemmed CHANGE IN INTESTINAL FLORA AND ITS ASSOCIATION WITH LIVER CYP2E1 IN MICE WITH LIVER INJURY INDUCED BY HIGH-INTENSITY ATORVASTATIN
title_short CHANGE IN INTESTINAL FLORA AND ITS ASSOCIATION WITH LIVER CYP2E1 IN MICE WITH LIVER INJURY INDUCED BY HIGH-INTENSITY ATORVASTATIN
title_sort change in intestinal flora and its association with liver cyp2e1 in mice with liver injury induced by high intensity atorvastatin
topic gastrointestinal microbiome|atorvastatin|chemical and drug induced liver injury|cytochrome p-450 enzyme system|rna, messenger|superoxide dismutase|lactobacillus
url https://jpmed.qdu.edu.cn/fileup/2096-529X/PDF/1701928426310-1484774633.pdf
work_keys_str_mv AT songbingxuesongyuqingliuxinyuhaichuxinhuilianghui changeinintestinalfloraanditsassociationwithlivercyp2e1inmicewithliverinjuryinducedbyhighintensityatorvastatin