首页|肉苁蓉苯乙醇苷对酒精性肝病模型小鼠脂质代谢稳态的改善作用及其机制

肉苁蓉苯乙醇苷对酒精性肝病模型小鼠脂质代谢稳态的改善作用及其机制

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目的:利用Lieber-Decarli液体酒精饲料构建小鼠酒精性肝病(alcoholic liver disease,ALD)模型,探究肉苁蓉苯乙醇苷(Cistanche deserticola phenylethanoid glycoside,CPhGs)对酒精性脂肪肝病脂质代谢稳态的调节作用.方法:将48 只雌性C57BL/6N小鼠随机分为对照组、对照+700 mg·kg-1 CPhGs组、模型组、模型+175 mg·kg-1 CPhGs组、模型+350 mg·kg-1 CPhGs组和模型+700 mg·kg-1 CPhGs组,每组8 只.基于美国国家酒精滥用与酒精中毒研究所(National Institute on Alcohol Abuse and Alcoholism,NIAAA)法构建小鼠ALD模型,建模成功后,不同浓度CPhGs灌胃给药,持续14 d.测定血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)含量.HE和油红O染色观察肝脏病理改变情况.用比色法检测肝脏匀浆中TG,TC,HDL-C和LDL-C含量.采用WB法检测肝脏组织中过氧化物酶体增殖物激活受体α(peroxisome proliferators activated receptor α,PPARα)蛋白量表达.结合LC-MS/MS技术对肝脏进行类靶向脂质代谢检测,筛选差异代谢物并进行代谢通路分析.结果:与模型组相比,模型+700 mg·kg-1 CPhGs组小鼠血清AST,ALT,TG,TC和LDL-C含量显著降低,HDL-C含量升高.HE与油红O染色结果显示,模型+700 mg·kg-1 CPhGs组肝脏脂滴蓄积明显降低.Western blot(WB)结果显示,与模型组相比,模型+700 mg·kg-1 CPhGs组PPARα蛋白表达量增加.脂质代谢共筛选出16 个差异代谢物,通路分析显示CPhGs主要通过调节甘油磷脂代谢、磷脂酰肌醇信号系统和磷酸肌醇代谢等代谢通路改善小鼠 ALD.结论:CPhGs 可以通过促进 PPARα 表达、增加磷脂酰胆碱(phosphatidylcholine,PC)类物质合成,调控相关脂质代谢通路,改善ALD脂质稳态.
Effect of Cistanche deserticola phenylethanoid glycoside on lipid metabolism homeostasis in alcoholic liver disease model mice and mechanism
Objective:Constructed a mouse model of alcoholic liver disease(ALD)using Lieber-Decarli liquid alcohol feed to investigate the regulation of lipid metabolism homeostasis in alcoholic fatty liver disease by Cistanche deserticola phenylethanoid glycoside(CPhGs).Methods:The 48 female C57BL/6N mice were randomly divided into control group,control + 700 mg·kg-1 CPhGs group,model group,model + 175 mg·kg-1 CPhGs group,model +350 mg·kg-1 CPhGs group and model +700 mg·kg-1 CPhGs group,with 8 mice in each group.The mouse model of alcoholic liver disease was established based on NIAAA method,and different concentrations of CPhGs were administered by gastric gavage for 14 days.Serum ALT,AST,TG,TC,HDL-C and LDL-C were detected.HE and oil red O staining were used to observe the pathological changes of liver.The contents of TG,TC,HDL-C and LDL-C in liver homogenate were detected by colorimetry.Western blot was used to detect the expression of PPARα protein in liver tissue.Combined with LC-MS/MS technology,targeted lipid metabolism in liver was detected,and differential metabolites were screened and the related metabolic pathways were analyzed.Results:Compared with the model group,the contents of serum AST,ALT,TG,TC and LDL-C in model +700 mg·kg-1 CPhGs group decreased significantly,while HDL-C increased.HE and oil red O staining results showed that the accumulation of liver lipid droplets decreased significantly in the model +700 mg·kg-1 CPhGs group.WB results showed that the expression of PPARα protein increased in the model +700 mg·kg-1 CPhGs group,compared to the model group.Sixteen different metabolites were screened from lipid metabolism,and the pathway analysis showed that CPhGs could improve alcoholic liver disease in mice mainly by regulating the metabolic pathways such as glycerophosphate metabolism,phosphatidylinositol signaling system and phosphoinositide metabolism.Conclusion:CPhGs can improve lipid homeostasis of ALD by promoting PPARα expression,increasing PC synthesis,regulating related lipid metabolism pathways.

Cistanche deserticola phenylethanolide glycosidealcoholic liver diseaselipid metabolism

许源慧、亓照耀、刘金存、孙红光、齐鑫鑫、从美丽、刘涛

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新疆医科大学公共卫生学院,乌鲁木齐 830011

肉苁蓉苯乙醇苷 酒精性肝病 脂质代谢

新疆维吾尔自治区自然科学基金重点项目国家级大学生创新创业训练计划

2022D01D36202210760174X

2024

中国新药杂志
中国医药科技出版社 中国医药集团总公司 中国药学会

中国新药杂志

CSTPCD北大核心
影响因子:1.039
ISSN:1003-3734
年,卷(期):2024.33(7)
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