中西医结合肝病杂志2025，Vol.35Issue(5)：564-570,7.DOI:10.3969/j.issn.1005-0264.2025.005.007
泽明红山方改善大鼠代谢相关脂肪性肝病合并脂肪酸代谢异常的机制研究
Study on the mechanism of Ze Ming Hong Shan prescription improving metabolic associated fatty liver disease with abnormal fatty acid metabolism in rats
摘要
Abstract
Objective:Ze Ming Hong Shan prescription is an empirical formula for the clinical treatment of metabolic associated fatty liver disease,which has a positive effect on regulating liver function and blood lipids in MAFLD patients.This study explores the effects and possible mechanisms of this formula on a rat model of MAFLD combined with mixed hyperlipidemia.Methods:SD rats were given high-fat diet for 8 weeks to establish a MAFLD combined with MHLP model.They were Randomly divided into model group,low and high dose Chinese medicine group,and fenofibrate group.Establish a model and administer corresponding medication interventions.Give regular feed as the control group.Observe the effects of drugs on the serology,liver pathology,cAMP-PKA signaling pathway mRNA,and fatty acid transport related protein expression of model rats.Results:First,the body weight and liver coefficient:There was no statistically significant difference in body weight among rats in each group;The weight and liver coefficient of the model group significantly increased,and the weight and liver coefficient of rats in each intervention group decreased to varying degrees,with the high-dose group showing the most significant decrease.Secondly,the liver function and blood lipids:Compared with the control group,the liver function(ALT,AST)and blood lipid levels(TG,TC,LDL-C,FFA)of the model group rats were significantly increased;Compared with the model group,the liver function and blood lipid levels of rats in each treatment intervention group were improved to varying degrees.Thirdly,the liver pathological staining:the liver lobule structure of the model group rats was unclear,with lipid droplets and vacuoles visible in the cytoplasm,accompanied by a large number of inflammatory cell infiltration,confirming that the liver exhibited diffuse steatosis.The morphology of liver cells and liver tissue structure showed varying degrees of improvement in each intervention group.Fourthly,the effect on the mRNA expression of cAMP,PKA,PPARα,and FABP1 in liver tissue:Compared with the control group,the gene expression levels of cAMP,PKA,and PPARα in the model group rats were significantly reduced,while the gene expression level of FABP1 was significantly increased;Compared with the model group,the gene expression levels in the liver of rats in each treatment intervention group were improved to varying degrees,with the high-dose group showing the most significant improvement.Fifthly,The effect of Western blot on the expression of FABP1 and CD36 proteins in liver tissue was detected:compared with the control group,the expression of FABP1 and CD36 proteins in the liver of the model group rats was significantly increased,and the protein expression of each intervention group was downregulated to varying degrees;The improvement effect of FABP1 and CD36 proteins in liver tissue of rats in the high and low dose groups was significant.Sixthly,the immunohistochemical method was used to detect the effects of cAMP,PPARα,and CD36 protein expression in liver tissue:Compared with the control group,the cAMP and PPARαprotein staining in the liver tissue of the model group rats was lighter,while the staining in each intervention group was darker than that in the model group.Compared with the control group,the CD36 protein staining in the liver tissue of the model group rats was deeper,and the staining in each intervention group was lighter than that in the model group.Conclusion:Zequ Mingshan Formula may promote the activation of PPARα protein,inhibit the expression of FABP1 and CD36,and lower serum levels of TG,TC,LDL-C,and FFA through the cAMP-PKA pathway.It can inhibit liver uptake of FFA,regulate liver lipid metabolism,alleviate liver cell inflammation,reverse liver damage,and play a role in treating MAFLD combined with MHLP.关键词
泽明红山方/代谢相关脂肪性肝病/混合型高脂血症/cAMP-PKA通路Key words
Ze Ming Hong Shan prescription/metabolic associated fatty liver disease/mixed hyperlipidemia/cAMP-PKA pathway分类
医药卫生引用本文复制引用
耿晓萱,卢秉久,郑佳连..泽明红山方改善大鼠代谢相关脂肪性肝病合并脂肪酸代谢异常的机制研究[J].中西医结合肝病杂志,2025,35(5):564-570,7.基金项目
全国名老中医药专家传承工作室建设项目(国中医药人教函[2022]75号),辽宁省科技厅省自然基金项目(No.2019-MS-231),辽宁省教育厅科学技术研究项目(No.L201903) （国中医药人教函[2022]75号）
