Objective To investigate the effect of tauroursodeoxycholic acid (TUDCA) on prevention of cholesterol gallstones formation in high-fat fed mice. Methods Thirty SPF grade male c57bl/6 mice were randomly divided into lithogenic diet (LD) group and TUDCA group. The mice in TUDCA group were fed 5g TUDCA/1 000 g LD. After 8 weeks of feeding, serum, gallbladder, liver and small intestine were collected and the formation of gallstones or crystals in gallbladder was examined. Composition of intestinal microbiota was examined. Gallbladder bile lipid composition, serum lipid and liver lipid in mice were detected. Expression of genes involved in bile acid and lipid metabolism of liver and small intestine was detected by quantitative real-time PCR. Results Cholesterol gallstones with cholesterol crystal formed in all mice of LD group (100%). Only cholesterol crystals were found in three mice without any gallstone in TUDCA group. The abundance of intestinal Firmicutes in TUDCA group (0.55%±0.06%) was higher than that in LD group (0.28%±0.02%)（P<0.01), while the abundance of Bacteroides in TUDCA group (0.05%±0.01%) was lower than that in LD group (0.30%±0.01%) (P<0.001). Compared with LD group, the ratio of Firmicutes/Bacteroides in TUDCA group increased by 3.13 times. Serum total cholesterol levels in TUDCA group [(2.36±0.11)mmol/L] decreased compared with that in LD group [(5.79±0.43)mmol/L] (P<0.01). Hepatic total cholesterol levels in TUDCA group [(4.12±0.21) mg/g] decreased significantly compared with that in LD group significantly[(83.17±3.06) mg/g] (P<0.001). mRNA expression level of Abcg5 and Abcg8 in liver of TUDCA group (6.32±0.26, 8.12±0.86) decreased significantly compared with that in LD group（9.48±0.64, 16.76±1.61）(P<0.01). The expression level of Abcb11 (15.74±1.06), Acat2 (2.04±0.02), Cyp27 (36.41±0.77) in the liver of TUDCA group increased compared with those in LD group (3.87±0.71, 1.47±0.09, 28.70±1.09）(P<0.001). Gallbladder cholesterol saturation index in TUDCA group (1.06±0.15) also decreased compared with that in LD group (2.40±0.36) (P<0.01). Conclusions TUDCA might inhibit the absorption and synthesis of lipids in small intestine by improving intestinal microbiota of high-fat fed mice, so as to reduce gallstone formation in the mice.
LU Qifan, JIANG Zhaoyan, WANG Qihan, ZHAO Gang, HU Hai
. Tauroursodeoxycholic acid prevents gallbladder stone formation in high-fat fed mice[J]. Journal of Surgery Concepts & Practice, 2019
, 24(06)
: 522
-529
.
DOI: 10.16139/j.1007-9610.2019.06.011
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