Relationship between expression of G-protein-coupled bile acid receptor 1 in gallbladder mucosa and lithogenic bile of gallstone / 中华肝胆外科杂志

ABSTRACT

Objective To study the relationship between expression of G-protein-coupled bile acid receptor 1 (GPBAR1) in gallbladder mucosa and formation of lithogenic bile in patients with gallstones.Methods Gallbladder mucosa,gallbladder wall,bile and plasma were collected from 34 patients with gallstone (GS) and 15 individuals who were gallstone free (GSF).The gallbladder wall was stained with hematoxylin-eosin (HE) and immunohistochemistry to detect pathologic changes and expressions of GPBAR1,mucin 1 (MUC1) and mucin 5AC (MUC5AC).Reverse-transcription polymerase chain reaction (RT-PCR) was used to test mRNA expressions of GPBAR1,MUC1 and MUC5AC in the gallbladder mucosa.The contents of total cholesterol (TC),total bile acid (TBA),triglyceride (TG),low density lipoprotein (LDL) and high density lipoprotein (HDL) in plasma and cholesterol,TBA,phospholipid (PL) and mucin in the bile of gallbladder were measured.Results The gallbladder mucosa in all GS patients showed chronic inflammation on hematoxylin-eosin staining.The expressions of GPBAR1 and MUC5AC were more markedly increased in the GS group than in the GSFgroup (61.34±8.06 vs.43.05±7.83,P＜0.01; 52.11±9.62 vs.45.05±9.27,P＜0.05).The mRNA expressions of GPBAR1 and MUC5AC in the GS group were also more markedly increased than in the GSR group (0.87±0.07 vs.0.80±0.09,P＜0.05; 1.04±0.22 vs.0.8±0.17,P＜0.01).Serum cholesterol,as well as biliary cholesterol,cholesterol mol percentage,cholesterol saturation index and mucin in the GS group were more significantly higher than in the GSF group (5.07±1.64 vs.3.62±1.42,P＜0.01; 17.23±3.67 vs.12.47±2.31,P＜0.01; 7.47±0.65 vs.5.05±0.24,P＜0.01; 1.03±0.58 vs.0.69±0.38,P＜0.01; 92.02±20.89 vs.76.36±19.71,P＜0.05).Biliary total bile acids and bile acids mol percentage were lower in the GS group than in the GSF group (162.68±20.19 vs.180.21±26.05,P＜0.05; 71.28±1.84 vs. 73.29±0.96,P＜0.01). In the GS group,there were negative correlations between the mRNA expression of GPBAR1 and biliary TBA (γ=-0.341,P＜0.05).There were negative correlations in the GS group between the GPBAR1 expression and the level of biliary TBA (γ=- 0.403,P＜0.05),and between the GPBAR1 expression and the level of biliary total lipid (γ=-0.365,P＜0.05).Conclusions This study shows an increase in expression of GPBAR1 in gallbladder mucosa in patients with GS.It is suggested that GPBAR1 may accelerate formation of lithogenic bile by inducing re-absorption of bile acid.