丹酚酸B调控脂质代谢改善非酒精性脂肪肝实验研究  

Experimental study on salvianolic acid B regulating lipid metabolism and improving non-alcoholic fatty liver

作　　者：张佳健 郭梦茹 梅金玉[2] 陈明 ZHANG Jia-jian;GUO Meng-ru;MEI Jin-yu;CHEN Ming(Dept of Pharmacology,School of Basic Medical Science,Anhui Medicine University,Hefei 230032,China;Dept of Otorhinolaryngology,Head and Neck Surgery,The Second Affiliated Hospital of Anhui Medical University,Hefei 230601,China)

机构地区：[1]安徽医科大学基础医学院药理学教研室,安徽合肥230032 [2]安徽医科大学第二附属医院耳鼻喉科,安徽合肥230601

出　　处：《中国药理学通报》2025年第1期107-115,共9页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金面上项目(No 82371541);安徽省研究生教育质量工程(No 2022zyxwjxalk060)。

摘　　要：目的探讨丹酚酸B(SalB)可能通过调控Lcn2改善非酒精性脂肪肝的作用。方法体内实验,8周龄♂C57BL/6J小鼠用普通维持饲料喂养,作为对照组,8周龄ApoE-/-小鼠用高脂饲料喂养,随机分为模型组和SalB组。在饲养8周后,SalB组小鼠用SalB灌胃,低剂量为15 mg·kg^(-1)·d^(-1),高剂量为30 mg·kg^(-1)·d^(-1),对照组和模型组用等剂量生理盐水灌胃。肝脏转录组测序结果揭示模型组和SalB组的差异表达基因,HE染色、油红O染色观察肝组织的病理变化,试剂盒检测血清和肝组织的脂质、氧化应激和炎症指标,RT-qPCR检测Lcn2、SREBP-1C以及脂质合成相关酶的mRNA水平。体外实验,用棕榈酸(PA)诱导L02和LX-2细胞24 h建立NAFLD模型,用SalB(30μmol·L^(-1))和PA(0.2 mmol·L^(-1))共孵育检测SalB体外改善NAFLD的情况。试剂盒检测L02细胞TC、TG的含量,细胞油红O染色试剂盒检测L02细胞的脂质积累,RT-qPCR检测LX-2细胞Lcn2、SREBP-1C以及脂质合成相关酶基因的mRNA水平。结果模型组血清、肝脏的生化指标异常,肝组织脂质、炎症和氧化应激水平升高,出现大面积脂肪空泡和大量的脂质沉积,PA诱导的L02细胞也出现大量的脂质积累,在SalB干预后均有明显改善。转录组测序结果表明SalB可以调控肝脏脂质代谢和炎症。肝脏和LX-2细胞mRNA水平显示模型组Lcn2、SREBP-1C以及脂质合成相关酶基因表达明显上调,SalB干预后均能降低这些基因的表达。结论丹酚酸B可以明显改善非酒精性脂肪肝,其机制可能是通过下调Lcn2、SREBP-1C和脂质合成酶的表达。Aim To explore the effect of salvianolic acid B(SalB)on improving non-alcoholic fatty liver by regulating Lcn2.Methods In vivo experiments,8-week-old male C57BL/6J mice were fed with regular maintenance diet as the control group,while 8-week-old ApoE-/-mice were fed with high-fat diet and randomly divided into the model group and SalB group.After eight weeks of feeding,mice in the SalB group were gavaged with SalB at a low dose of 15 mg·kg^(-1)·d^(-1) and a high dose of 30 mg·kg^(-1)·d^(-1),while mice in the control and model groups were gavaged with equal doses of normal saline.The results of liver RNA-seq revealed differentially expressed genes between the model group and the SalB group.HE staining and Oil Red O staining were used to observe pathological changes in liver tissue.The kit was used to detect lipid,oxidative stress,and inflammation in serum and liver tissue.RT-qPCR was employed to detect the mRNA levels of Lcn2,SREBP-1C,and enzymes related to lipid synthesis.In vitro experiments established a NAFLD model by inducing L02 and LX-2 cells with palmitic acid(PA)for 24 hours,and the effect of SalB on non-alcoholic fatty liver in vitro was detected by co treatment of SalB(30μmol·L^(-1))and PA(0.2 mmol·L^(-1)).The assay kit was used to detect the content of TC and TG in L02 cells,the cell oil red O staining to detect the accumulation of lipids in L02 cells,and RT-qPCR to detect the mRNA levels of Lcn2,SREBP-1C,and genes related to lipid metabolism in LX-2 cells.Results The biochemical indicators of serum and liver in the model group were abnormal,with elevated levels of lipid,inflammation,and oxidative stress in liver tissue.Large areas of lipid vacuoles and deposition were observed,and PA induced L02 cells also exhibited significant lipid accumulation.These liver lesions were significantly improved after intervention with SalB.The effect of SalB on regulating lipid metabolism and inflammation was found from RNA-seq.The mRNA levels of liver and LX-2 cells showed significant upregulation of Lcn2,SREBP

关 键 词：SalB 非酒精性脂肪肝 脂质代谢 Lcn2 SREBP-1C 脂质合成相关酶 

分 类 号：R285.5[医药卫生—中药学]