[Mechanism of Dahuang Lingxian Capsule for Regulating and Controlling Expression of Hepatocyte Transporters and Bile Metabolism Spectrum in Gallstone Mice].

Objective To observe the effects of Dahuang Lingxian Capsule (DLC) for regulating and controlling expression of hepatocyte transporters and bile metabolism spectrum in gallstone mice u- sing Western blot and gas chromatography-mass spectrometer ( GC-MS) , and to explore its possible mechanism. Methods Fifty male C57BL/6 mice were randomly divided into five groups, i.e., the normal control group (N), the model group (M) , the ursodeoxycholic acid (UDCA) control group (U) , the drug control group (Y) ,the DLC treatment group (D) , 10 in each group. Mice in group N and group Y were fed with common forage. Forage with high fat, high calorie, high cholesterol was fed to mice in group M, U, and D to induce cholecystolithiasis. Meanwhile, UDCA solution (130 mg kg⁻¹ - d⁻¹) was administered to mice in group U by gastrogavage. DLC decoction (13 g - kg⁻¹ - d1) was administered to mice in group Y and D by gastrogavage. Equal volume of normal saline was administered to mice in group N and M by gastrogavage. After 8-week intervention, gallstone formation rate was observed. Changes of ATP binding cassette subfamily B member 11 (Abcb1l ) and ATP binding cassette subfamily C member 2 (Abcc2) were observed using Western blot. Metabonomic features were detected by GC-MS. Results Improper operation occurred during modeling. One mouse died in group U since its esophagus was pricked by lavage needle. The gallstone formation rate was 100. 00% , higher than that in group N and Y (0.00%, 0.00%; x² =20. 00,P <0. 01). Compared with group M, the gallstone formation rate was reduced in group U and D (44. 44%, x² =7. 54,P = 0. 011 ; 30. 00%, X² = 10. 77, P 0. 003). Cholesterol characteristic absorption peak could be seen at 2 939, 1 446, 1 382, and 1 056 cm - after infrared spec- trum analysis. There was statistical difference in Abcbl1 and Abcc2 among the 5 groups (F =41. 89, P < 0. 01; F=90. 01 , P <0. 01). Compared with group N, expressions of Abcb1 1 and Abcc2 transporters sig- nificantly decreased in group M (P <0. 01). Compared with group M, expressions of Abcb11 and Abcc2 transporters significantly increased in group U, Y, D (P <0. 01). Compared with other groups, concentrations of endogenous metabolites such as alanine, citric acid, lysine, methionine, phenylalanine, tyrosine, cholesterol, low-density lipoprotein (LDL), glycerine, malic acid, acetone increased; concentrations of lactic acid, glutamine, amine glycine, choline, and taurine decreased (P <0. 05, P <0. 01). Con- clusion DLC could stabilize expression of Abcb1 1 and Abcc2, change or improve pathological secretion of bile and its metabolites, thereby achieving the effect of gallstone prevention and treatment.