首页|基于转录组与代谢组学联合分析探讨加减酸梅汤治疗代谢相关脂肪性肝病作用机制

基于转录组与代谢组学联合分析探讨加减酸梅汤治疗代谢相关脂肪性肝病作用机制

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目的:研究加减酸梅汤对代谢相关脂肪性肝病(Metabolic associated fatty liver disease,MAFLD)的疗效及机制。方法:C57BL6 J小鼠随机分成正常小鼠和模型小鼠,采用高脂饲料喂养造模12 w,造模成功后将模型小鼠随机分为模型对照组、加减酸梅汤0。55、1。1、2。2 g/kg组和二甲双胍0。10 g/kg组,每组6只。观察小鼠治疗前后体质量变化、治疗后肝质量及肝指数;采用生化法检测血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)及肝脏TC、TG含量;HE和油红O染色分别观察肝脏病理和脂质沉积情况;转录组学及代谢组学观察小鼠基因及肝脏小分子代谢物的变化;RT-qPCR检测肝脏Pi3k和Akt mRNA表达。结果:与正常对照组比较,模型对照组小鼠体质量增加,肝指数增加,血清TC、TG、LDL-C含量和肝脏TC、TG含量明显升高,血清HDL-C含量降低,肝脏出现脂肪样变及大量脂滴,肝脏Pi3k和Akt mRNA表达明显上调(P<0。05);与模型对照组比较,加减酸梅汤各组小鼠体质量、肝质量减轻,肝指数降低,血脂降低,肝脏病理学显示小鼠肝脏脂质沉积减轻,脂滴减少;转录组学KEGG富集分析表明,加减酸梅汤改善MAFLD可能与脂代谢和炎症相关的通路有关,肝脏Pi3k和Akt mRNA表达明显下调(P<0。05)。结论:加减酸梅汤可以改善小鼠MAFLD,其机制可能与抑制PI3K-AKT通路有关。
Mechanism of Modified Suanmei Decoction in the Treatment of MAFLD Based on Transcriptomics and Metabolomics
Objective:To investigate the therapeutic effect and mechanism of modified Suanmei Decoction on metabolic-associated fatty liver disease (MAFLD).Methods:C57BL6 J mice were randomly divided into normal mice and model mice.The model mice were fed a high-fat diet for 12 weeks to induce MAFLD.After successful modeling,the model mice were randomly divided into model control group,modified Suanmei Decoction groups (0.55,1.1,and 2.2 g/kg),and metformin group (0.10 g/kg),with 6 mice in each group.Changes in body weight be-fore and after treatment,liver weight,and liver index after treatment were observed.Biochemical methods were used to detect serum total cholesterol (TC),triglycerides (TG),low-density lipoprotein (LDL-C),high-density lipoprotein (HDL-C),and liver TC and TG levels.HE and oil red O staining were used to observe liver pathology and lipid deposition.Transcriptomics and metabolomics were employed to ex-amine changes in gene expression and small molecule metabolites in the liver.RT-qPCR was used to detect the expression of Pi3k and Akt mRNA in the liver.Results:Compared with the normal control group,the model control group showed an increase in body weight and liver index,significantly higher levels of serum TC,TG,LDL-C,and liver TC and TG,and decreased serum HDL-C.Fatty degeneration and nu-merous lipid droplets were observed in the liver,and Pi3k and Akt mRNA expression was significantly upregulated (P<0.05).Compared with the model control group,the modified Suanmei Decoction groups showed reduced body weight,liver weight,liver index,and blood lipid levels.Liver pathology indicated a reduction in lipid deposition and fewer lipid droplets in the liver tissue.Transcriptomic KEGG enrichment analysis suggested that the improvement of MAFLD by modified Suanmei Decoction may be related to pathways involving lipid metabolism and inflammation,with a significant decrease in Pi3k and Akt mRNA expression in the liver (P<0.05).Conclusion:Modified Suanmei Decoc-tion can improve MAFLD in mice,and its mechanism may be related to the inhibition of the PI3K-AKT pathway.

Modified Suanmei DecoctionMetabolic-associated fatty liver diseaseTranscriptomicsMetabolomicsPI3KAKT

赵美、张永、罗雅琪、杨炀、党思捷、何蕴良、郭志清、张钟艺、赵相雨

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成都中医药大学基础医学院,成都 611137

四川省中医药科学院中医研究所(四川省第二中医医院),成都 610031

成都中医药大学附属医院,成都 610072

加减酸梅汤 代谢相关性脂肪性肝病 转录组学 代谢组学 磷酯酰肌醇激酶 蛋白激酶

2024

中药药理与临床
中国药理学会 四川省中医药科学院

中药药理与临床

北大核心
影响因子:0.996
ISSN:1001-859X
年,卷(期):2024.40(9)