猪胆粉有效成分 HDCA通过调控肠道胆汁酸代谢抑制胆固醇结石形成的实验研究OA

AIM:To explore how hyodeoxycholic acid(HDCA)regulates intestinal bile acid metabolism and thereby modulates the activity of farnesoid X receptor(FXR)to inhibit the formation of cholesterol gallstones.METHODS:The C57BL/6J mice were randomly divided into a control group,a cholesterol gallstone model group,and a Pulvis fel-lis suis(PFS)(7%,10%)administration intervention group(6 mice in each group).The C57BL/6J mice were also randomly divided into a control group,a cholesterol gallstone model group,and HDCA(0.1%,0.5%,1%)administration intervention groups(6 mice in each group).The mice in each group were weighed,photographed,and tissue samples were collected for gallstone grade assessment.The total cholesterol(T-CHO)content in the samples was de-tected using a total cholesterol detection kit and a microplate reader.In the in vitro cell experiments,the direct regulatory effect of HDCA on FXR in in-testinal cells was analyzed by quantitative poly-merase chain reaction(qPCR).The differences in fe-cal microbiota among the groups were detected us-ing 16S ribosomal RNA(16S rRNA)sequencing tech-nology.The changes in the bile acid pool in the ileum tissue were determined by liquid chromatog-raphy-mass spectrometry(LC-MS/MS).RESULTS:Compared with the model group,both the 10%PFS and 1%HDCA intervention groups significantly re-duced the grade of cholesterol gallstones in the gallbladder and the serum cholesterol content of mice(P<0.01),and the 1%HDCA group significantly decreased the ratio of liver weight to body weight and the cholesterol content in the liver of mice(P<0.01);in the in vitro experiments,HDCA signifi-cantly reduced the relative expression level of FXR in intestinal cells Caco-2(P<0.05,P<0.01);HDCA sig-nificantly reduced the content of the Verrucomicro-biota(which was significantly positively correlated with activated FXR-type bile acids)(P<0.05)and sig-nificantly increased the content of the Bacteroidota(which was significantly negatively correlated with activated FXR-type bile acids)(P<0.01).Moreover,HDCA significantly changed the composition of in-testinal bile acids,reducing the proportion of acti-vated FXR-type bile acids and increasing the propor-tion of inhibitory FXR-type bile acids(P<0.05).CON-CLUSION:HDCA may increase the inhibition of FXR-type bile acids by regulating the intestinal flora,thereby indirectly exerting the effect of inhibiting intestinal FXR,promoting bile acid synthesis and re-ducing cholesterol saturation,and achieving the goal of inhibiting the formation of cholesterol gall-stones.