miR-199a-5p promotes bile duct ligation-induced liver fibrosis of rats by regulating intestinal microbiota
10.19405/j.cnki.issn1000-1492.2024.10.014
- VernacularTitle:miR-199a-5p通过调节肠道菌群促进胆总管结扎诱导的大鼠肝纤维化
- Author:
Xiaoyan CUI
1
;
Xiaohan YU
;
Jing ZHOU
;
Luyao WANG
;
Ronghua ZHANG
;
Meimei WANG
;
Yanan XIONG
;
Zhiyong LIU
;
Guangling ZHANG
Author Information
1. 华北理工大学基础医学院,河北省慢性疾病重点实验室,唐山 063210
- Keywords:
miR-199a-5p;
intestinal microbiota;
bile duct ligation;
liver fibrosis;
inflammation
- From:
Acta Universitatis Medicinalis Anhui
2024;59(10):1794-1801
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of miR-199a-5p on common bile duct ligation(BDL)-induced liver fibrosis in rats by regulating intestinal flora.Methods The 25 SD rats were randomly divided into five groups:the Sham group,the BDL group,the negative control adenovirus(NC adv)group,the miR-199a-5p adv group and the miR-199a-5p sponge adv group.The pathological changes of liver tissue and the degree of liver fibrosis were ob-served by HE,Masson and Sirius Red staining.The levels of aspartate aminotransferase(AST),alanine amin-otransferase(ALT),total bilirubin(TBIL)and direct bilirubin(DBIL)in serum of rats were determined by a fully automatic biochemical analyzer.The mRNA expression level of miR-199a-5p in liver tissue of rats was detec-ted by qRT-PCR.The protein expression levels of α-smooth muscle actin(α-SMA)and collagen type 1 alpha 1(COL1A1)in liver tissue of rats were detected by double immunofluorescence staining and Western blot experi-ment.Rat feces were collected for 16S rRNA high-throughput sequencing.Results The expression of miR-199a-5p was up-regulated in the liver tissue of BDL rats(P<0.01).Compared with the NC adv group,the degree of liver injury and collagen deposition were relatively serious,the levels of AST,ALT,TBIL and DBIL in serum and the expression levels of α-SMA and COL1A1 in liver tissue increased in the miR-199a-5p adv group(all P<0.05).However,the results of miR-199a-5p sponge adv intervention were opposite(all P<0.05).The 16S rRNA sequencing results showed that rats treated with miR-199a-5p adv were characterized by increased diversity and richness of intestinal microbiota,changed composition of intestinal microbiota,while the results of miR-199a-5p sponge adv interfering with the bacterial community were opposite(all P<0.05).Conclusion miR-199a-5p promotes liver fibrosis of BDL rats,and its mechanism may be related to regulating the diversity and abundance of intestinal microbiota.