A Study Of The Relationship Between The Expression Of TGR5 In Gallbladder Mucosa And The Lithogenic Bile Of Gallstone

Objective:To study the relationship between expression of TGR5 in gallbladder mucosa and formation of the lithogenic bile in gallstone patients, and to reinforce cause of cholesterolcalculus.Methods:The gallbladder bile and the gallbladder tissue of 49 patients who underwent laparoscopic or open cholecystectomy were harvested. There are 34 patients with gallstone (GS) and 15 patients with control. The gallbladder wall was used hematoxylin-eosin (HE) staining and immunohistochemistry to observe the pathologic changes and the protein expression of TGR5, MUC1 and MUC5AC. The gallbladder mucosa was used reverse-transcription polymerase chain reaction (RT-PCR) to test the mRAN expression of TGR5, MUC1 and MUC5AC. The contents of total cholesterol (TC), total bile acid (TBA), Triglyceride (TG), low density lipoprotein (LDL) and high density lipoprotein (HDL) in preoperative plasma and cholesterol, TBA, phospholipid (PL) and mucin in bile of gallbladder were measured.Results:(1) The gallbladder mucous in all GS patients has chorine inflammation by hematoxylin-eosin staining. (2) TGR5 was localized in the apical domain of gallbladder epithelial cells. MUC1 were localized in the cytoplasm of gallbladder epithelial cells. MUC5AC were localized in the apical domain and cytoplasm of gallbladder epithelial cells. The receptor expression TGR5 and MUC5AC was increase markedly in GS group than control (t=7.498, P<0.01 and t=2.392, P<0.05). (3) The mRNA expression of TGR5 and MUC5AC in GS group were increase markedly than control (t=2.652, P< 0.05 and t=3.079,P<0.01). (4) Serum TC (t=2.974,P<0.01), as well as biliary cholesterol (t-4.610, P<0.01), cholesterol mol percentage (t=14.004, P<0.01), cholesterol saturation index (t=20.752, P<0.01) and mucin (t=2.459, P<0.05) in GS group was increased markedly than control. Biliary total bile acids (t=-2.558, P<0.05) and bile acids mol percentage (t=-3.984, P<0.01) were lower in GS than control. (5) There were positive correlations, in GS patients group, between mRNA expression of TGR5 and their receptor expression (y=0.669, P<0.01), between mRNA expression of MUC5AC and their receptor expression (y= 0.898 P<0.01). In GS group, there were negative correlations between mRNA expression of TGR5 and biliary TBA (y=-0.341, P<0.05). There were negative correlations, in GS patients group, between TGR5 receptor expression and level of biliary TBA (y=-0.403, P<0.05), between TGR5 receptor expression and level of biliary total lipid (y=-0.365, P<0.05).Conclusions:This study shows that the increased expression of TGR5 in gallbladder mucosa of patients with GS, results in advance the re-absorption of bile acid to accelerate the serum bile acid level. Then it feedback inhibition synthesize of bile acid, results in synchronization enhance cholesterol of serum and biliary, but decline total bile acid of biliary to keep the hypersaturation of biliary. Chronic inflammation and elevation of intracellulare bile acid concentration in the gallbladder mucosa which result from the over-expression of TGR5, possibly promote mucin gene over-expression such as MUC5AC. Mucin which facilitates hypersaturation biliary to form crystal nucleation is greatly secreted into biliary. It is suggested that TGR5 and MUC5AC may accelerate the formation of lithogenic bile through induced the re-absorption of bile acid and mucin overproduction.