摘要
目的基于KLF16/PPAR-α信号通路探讨参苓白术散对代谢相关脂肪性肝病(MAFLD)小鼠肝脏脂质代谢的影响。方法将C57BL/6小鼠随机分为正常组、模型组及参苓白术散低、中、高剂量组(2.685、5.369、10.738 g·kg^(-1)·d^(-1)),每组7只。除正常组给予标准饲料外,其余各组小鼠均给予高脂饲料连续喂养12周,复制MAFLD模型。造模结束后开始灌胃给药,每日1次,连续5周。测定小鼠体质量及肝脏系数;采用HE及油红O染色观察小鼠肝脏组织病理变化;检测血清谷氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、甘油三酯(TG)及总胆固醇(TC)水平;RT-qPCR法检测肝组织中PPAR-α、KLF16、FAS、SREBP-1c mRNA表达水平。结果与正常组比较,模型组小鼠的体质量、肝质量及肝脏系数明显升高(P<0.05,P<0.01);血清TG、TC、ALT、AST水平显著升高(P<0.001);肝细胞胞质可见大量空泡,出现大量红染的脂滴,NAS病理评分及油红O染色IOD值显著升高(P<0.05,P<0.001);肝组织中PPAR-α、KLF16 mRNA表达显著下调(P<0.01,P<0.001),FAS、SREBP-1c mRNA表达显著上调(P<0.05,P<0.001)。与模型组比较,参苓白术散高剂量组小鼠的体质量、肝质量、肝脏系数明显降低(P<0.05);参苓白术散低、中、高剂量组小鼠的血清TG、TC、ALT水平显著降低(P<0.05,P<0.01,P<0.001);参苓白术散中、高剂量组小鼠的血清AST水平显著降低(P<0.01,P<0.001);各给药组小鼠肝组织病理变化有明显改善,肝细胞胞质内橘红色脂滴显著减少,参苓白术散高剂量组的NAS病理评分及油红O染色IOD值显著降低(P<0.05,P<0.01);参苓白术散低、中、高剂量组小鼠肝组织中PPAR-α、KLF16 mRNA表达显著上调(P<0.05,P<0.01,P<0.001),FAS、SREBP-1c mRNA表达显著下调(P<0.05,P<0.01,P<0.001)。结论参苓白术散对MAFLD小鼠的肝脏脂质代谢有明显改善作用,其机制可能与转录调控核受体KLF16/PPAR-α信号通路有关。
Objective To investigate the effects of Shenling Baizhu San on hepatic lipid metabolism in mice with metabolic associated fatty liver disease(MAFLD)based on the KLF16/PPAR-αsignaling pathway.Methods C57 BL/6 mice were randomly divided into normal group,model group and Shenling Baizhu San low-,medium-and high-dose groups(2.685,5.369,10.738 g·kg^(-1)·d^(-1)),with seven mice in each group.Except for the normal group,the mice in the other groups were given high-fat diet for 12 weeks to replicate the MAFLD model.After the modeling,intragastric administration was started once a day for five weeks.The body mass and liver coefficient of mice were measured.HE and oil red O staining were used to observe the pathological changes of liver tissue in mice.The levels of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),triglyceride(TG)and total cholesterol(TC)were detected.The mRNA expression levels of PPAR-α,KLF16,FAS and SREBP-1c in liver tissue were detected by RT-qPCR.Results Compared with the normal group,the body mass,liver mass and liver coefficient of mice in the model group were significantly increased(P<0.05,P<0.01).The levels of serum TG,TC,ALT and AST were significantly increased(P<0.001).There were a large number of vacuoles in the cytoplasm of the liver tissue,and a large number of red-stained lipid droplets appeared in the cytoplasm.The NAS pathological score and oil red O staining IOD value were significantly increased(P<0.05,P<0.001).The mRNA expressions of PPAR-αand KLF16 in liver tissue were significantly down-regulated(P<0.01,P<0.001),and the mRNA expressions of FAS and SREBP-1c was significantly up-regulated(P<0.05,P<0.001).Compared with the model group,the body mass,liver mass and liver coefficient of mice in the high-dose group of Shenling Baizhu San were significantly decreased(P<0.05).The levels of serum TG,TC and ALT in the low-,medium-and high-dose groups of Shenling Baizhu San were significantly decreased(P<0.05,P<0.01,P<0.001).The serum AST level of mice in the medium-and high-dose groups of Shenling Baizhu San was significantly decreased(P<0.01,P<0.001).The pathological changes of liver tissue in each administration group were significantly improved,and the orange-red lipid droplets in the cytoplasm of hepatocytes were significantly reduced.The NAS pathological score and oil red O staining IOD value of the high-dose group of Shenling Baizhu San were significantly reduced(P<0.05,P<0.01);the mRNA expressions of PPAR-αand KLF16 in liver tissue of mice in Shenling Baizhu San low-,medium-and high-dose groups were significantly up-regulated(P<0.05,P<0.01,P<0.001),and the mRNA expressions of FAS and SREBP-1c were significantly down-regulated(P<0.05,P<0.01,P<0.001).Conclusion Shenling Baizhu San can significantly improve hepatic lipid metabolism in MAFLD mice,and its mechanism may be related to transcriptional regulation of nuclear receptor KLF16/PPAR-αsignaling pathway.
作者
黄尚一
陈稼炳
李佳雨
周凯莉
易钦澄
高永
HUANG Shangyi;CHEN Jiabing;LI Jiayu;ZHOU Kaili;YI Qincheng;GAO Yong(Science and Technology Innovation Center,Guangzhou University of Chinese Medicine,Guangzhou 510405 Guangdong,China)
出处
《中药新药与临床药理》
CAS
CSCD
北大核心
2024年第8期1163-1169,共7页
Traditional Chinese Drug Research and Clinical Pharmacology
基金
国家自然科学基金面上项目(82070891)
广州市科技局民生科技项目(202002020032)
广州市基础与应用基础研究项目(202201011501)。
作者简介
黄尚一,男,硕士研究生,研究方向:糖脂代谢紊乱机制研究及中医药干预。Email:609910956@qq.com。;通信作者:高永,男,研究员,教授,博士研究生导师,研究方向:糖脂代谢紊乱机制研究及中医药干预。Email:gaoyong@gzucm.edu.cn。
