The Effect Of Baicalin On Gallstone Formation In Mice And Its Underlying Mechanism

Objective: Gallstones are diseases caused by abnormal bile components and dysfunctional biliary motility.They are common and frequently-occurring diseases,often manifested as abdominal pain,nausea,vomiting and other symptoms.Cholesterol metabolic disorders,lipid metabolism,abnormal transport and secretion,and poor living habits are all important predisposing factors for gallstone disease.It is also because of the many predisposing factors that the pathogenesis of gallstone disease remains to be further elucidated.Regarding the treatment of gallstone disease,drug treatment,lithotripsy,and surgical treatment are commonly used treatments at present,but there are still many problems to be solved in the above treatment methods.Therefore,further exploration and clarification of the pathogenesis of gallstone disease,and the use of this as a breakthrough to develop more effective treatments is of great significance in the fight against gallstone disease,and the aim of this study was to investigate the therapeutic effects of baicalin on experimental cholesterol gallstones in mice.Methods: The mouse gallstone model was established by feeding on the lithogenic diet.The mice were divided into five groups: A: control group,B: high dose of baicalin,C: gallstone group,D: gallstone + baicalin high dose Group,E: gallstone + baicalin low dose group.The formation of cholesterol stones was then observed in the gallbladder and the hyperplasia and inflammatory infiltration were observed in the gallbladder wall of gallstone mice.Triglyceride(TG)in bile,total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C)and total bile acid(TBA)in mice were detected and the content was compared in different groups.Real-time PCR and Western blot were used to detect the protein and mRNA expression levels of CYP7a1,CYP8b1,ABCG5,ABCG8 and LXRα in the liver of mice with gallstones.Then,HE staining was used to observe the cell necrosis and inflammatory infiltration caused by the lithogenic diet,and the enzyme activities of two markers of liver damage,ALT and AST,were also examined.The expression of several inflammatory factors including TNF-α,IL-1β and IL-6 was determined by ELISA,and the state transition of malondialdehyde(MDA)content and superoxide dismutase(SOD)activity was also observed.Finally,the liver X receptor alpha(LXRα)agonist T0901317 was used to observe its effect on the therapeutic effect of baicalin.Results: The lithogenic diet resulted in elevated serum triglycerides,cholesterol,low-density lipoprotein levels,and decreased high-density lipoprotein levels.Hyperplasia and inflammatory infiltration were observed in the gallbladder wall of gallstone mice.We also found that the cholesterol in the bile of mice fed with lithogenic diet increased and the bile acid decreased.The results of real-time PCR and Western blot showed that the expression levels of two enzymes catalyzing the synthesis of bile acids in the liver of gallbladder stones were decreased,while the expression levels of the two cholesterol transporters were increased.The lithogenic diet also leads to increased activity of alanine aminotransferase and aspartate aminotransferase in serum,elevated levels of TNF-α,IL-1β,IL-6 and MDA,and decreased SOD activity in the liver.Inflammation and oxidative stress were shown.In addition,we also observed an increase in LXRα in the liver.After the use of baicalin,gallstones,hyperlipidemia,gallbladder hyperplasia,liver inflammation and oxidative stress,and abnormal cholesterol metabolism caused by calculous diet were all relieved to some extent.At the same time,baicalin can also inhibit the expression of LXRα in the liver.In addition,the LXRα agonist T0901317 exacerbated the harmful effects of the lithogenic diet on mice.Conclusion: The successful lithogeni diet leads to the production of gallstones in mice,and shows inflammation and oxidative stress.The use of baicalin can alleviate gallstones,hyperlipidemia,gallbladder hyperplasia liver inflammation,oxidative stress and abnormal cholesterol metabolism caused by lithogeni diet to some extent.,.At the same time,baicalin can also inhibit the expression of LXRα in the liver.The use of the LXRα agonist T0901317 aggravated the deleterious symptoms of the lithogeni diet in mice,demonstrating that baicalin may play a protective role in a gallstone-induced gallstone mouse model by inhibiting LXRα activity.