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丹酚酸B调控脂质代谢改善非酒精性脂肪肝实验研究

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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(30 μmol·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.
Experimental study on salvianolic acid B regulating lipid metabolism and improving non-alcoholic fatty liver
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 random-ly divided into the model group and SalB group.After eight weeks of feeding,mice in the SalB group were ga-vaged 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 chan-ges in liver tissue.The kit was used to detect lipid,ox-idative stress,and inflammation in serum and liver tis-sue.RT-qPCR was employed to detect the mRNA lev-els 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 treat-ment of SalB(30 pmol·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-1 C,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 tis-sue.Large areas of lipid vacuoles and deposition were observed,and PA induced L02 cells also exhibited sig-nificant lipid accumulation.These liver lesions were significantly improved after intervention with SalB.The effect of SalB on regulating lipid metabolism and in-flammation was found from RNA-seq.The mRNA lev-els of liver and LX-2 cells showed significant upregula-tion of Lcn2,SREBP-1 C,and enzymes related to lipid metabolism in the model group,and markedly downreg-ulation in the SalB group.Conclusions SalB can im-prove non-alcoholic fatty liver,and its mechanism may be related to down-regulating the expression of Lcn2,SREBP-1 C,and lipid synthase.

SalBnon-alcoholic fatty liver diseaselipid metabolismLcn2SREBP-1Cenzymes related to lipid metabolism

张佳健、郭梦茹、梅金玉、陈明

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安徽医科大学基础医学院药理学教研室,安徽 合肥 230032

安徽医科大学第二附属医院耳鼻喉科,安徽 合肥 230601

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

2025

中国药理学通报
中国药理学会

中国药理学通报

北大核心
影响因子:1.54
ISSN:1001-1978
年,卷(期):2025.41(1)