Effects of Longdan Xiegan Decoction on cholesterol metabolism in gallbladder cholesterol stone mice
Objective:The effect of Longdan Xiegan Decoction on cholesterol metabolism in cholesterol stone(CS)mice was investigated through the expression changes of closely related genes NPC1L1,ABCG5 and ABCG8.Methods:A total of 32 male C57BL/6J mice were randomly divided into a blank group(n=12)and a model group(n=20).CS mouse models were established using lithogenic feed induction method.After 8 weeks,4 mice from each group were randomly selected to observe the condition of gallbladder stones.After successful modeling,the modeling group was randomly divided into model group(8 mice)and Longdan Xiegan Decoction group(8 mice).The Longdan Xiegan Decoction group was orally administered with Longdan Xiegan Decoction 13.8 g·kg-1·d-1,while the blank group and model group were orally administered with equal amounts of physiological saline for 4 weeks of intervention.Tissue morphology of the liver and small intestine of each group of mice were observed by using hematoxylin eosin staining.ELISA was used to detect serum cholesterol(TC)and triglycerides(TG),as well as bile TC and bile acid(TBA)levels.The mRNA and protein expression levels of NPC1L1 and ABCG5/ABCG8 were detected by q-PCR and Western Blot in mouse liver and small intestine tissues,respectively.Results:Compared with the blank group,the serum TC,TG,and bile TC,TBA of the model group mice increased significantly(P＜0.01,P＜0.05),the mRNA and protein expression of NPC1L1 in the small intestine of the model group were significantly upregulated(P＜0.01),while the mRNA and protein expression of ABCG5/G8 were significantly downregulated(P＜0.01),the mRNA and protein expression of NPC1L1 in liver tissue were significantly downregulated(P＜0.01),while the mRNA and protein expression of ABCG5/G8 were significantly upregulated(P＜0.01).Compared with the model group,the pathological morphology of the liver and small intestine tissues in the Longdan Xiegan Decoction group was significantly improved,the serum TC,TG,and bile TC,TBA in the Longdan Xiegan Decoction group were significantly reduced(P＜0.01,P＜0.05),the mRNA and protein expression of small intestine NPC1L1 in the Longdan Xiegan Decoction group were significantly downregulated(P＜0.01,P＜0.05),while the mRNA and protein expression of small intestine ABCG5/G8 were significantly upregulated(P＜0.01,P＜0.05),the mRNA and protein expression of liver NPC1L1 was significantly upregulated(P＜0.01),while the mRNA and protein expression of liver ABCG5/G8 were significantly downregulated(P＜0.05,P＜0.01).Conclusion:Longdan Xiegan Decoction can improve abnormal cholesterol metabolism in CS model mice.Abnormal expression of NPC1L1 and ABCG5/G8 in intestinal and liver tissues may lead to cholesterol susaturation,which may be one of the molecular basis of CS damp-heat accumulation.
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