基于SQLE/CA3/SREBP1c途径研究绞股蓝皂苷改善非酒精性脂肪肝病的机制

doi:10.16333/j.1001-6880.2025.4.011

天然产物研究与开发 ›› 2025, Vol. 37 ›› Issue (4): 687-693.doi: 10.16333/j.1001-6880.2025.4.011 cstr: 32307.14.1001-6880.2025.4.011

基于SQLE/CA3/SREBP1c途径研究绞股蓝皂苷改善非酒精性脂肪肝病的机制

孙小扉，宋囡，曹媛，杨莹，朱敬轩，高浩，王嘉鑫，贾连群*

辽宁中医药大学，沈阳 110847

出版日期:2025-04-30 发布日期:2025-04-27
基金资助:
国家自然科学基金(82374423，82074145)

Mechanism of gypenoside in improving non-alcoholic fatty liver disease based on SQLE/CA3/SREBP1c pathway

SUN Xiao-fei, SONG Nan, CAO Yuan, YANG Ying, ZHU Jing-xuan, GAO Hao, WANG Jia-xin, JIA Lian-qun*

Liaoning University of Traditional Chinese Medicine, Shenyang 110847, China

Online:2025-04-30 Published:2025-04-27

摘要/Abstract

摘要：

研究绞股蓝皂苷(gypenosides，GPs)改善肝脏脂质沉积情况，进而防治非酒精性脂肪肝病(nonalcoholic fatty liver disease，NAFLD)的作用，并探究其潜在的机制。将12只ApoE-/-小鼠按随机数字表法分为模型组(model，Mod)、GPs组，6只C57BL/6J小鼠作为空白对照组(control，Con)。正常饲料喂养Con组，其余各组高脂饲料喂饲12周。绞GPs组按2.97 g/(kg·d)灌胃，Con组和Mod组等体积生理盐水灌胃，共4周。全自动生化分析仪检测小鼠血清甘油三酯(triglycerides，TG)、总胆固醇(total cholesterol，TC)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol，LDL-C)、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol，HDL-C)水平，苏木素-伊红(hematoxylin-eosin，HE)染色观察小鼠肝脏病理形态学变化，油红O染色观察小鼠肝脏脂质沉积情况，ELISA检测各组小鼠肝脏TG、游离脂肪酸(free fatty acid，FFA)含量，实时荧光定量PCR法及Western blot法检测肝脏角鲨烯环氧化酶(squalene epoxidase，SQLE)、碳酸酐酶Ⅲ(carbonic anhydrase Ⅲ，CA3)、固醇调节元件结合蛋白lc(sterol regulatory element binding protein-lc，SREBP1c)、乙酰辅酶A羧化酶(acetyl coenzyme A carboxylase，ACC)、脂肪酸合成酶(fatty acid synthase，FASN)、硬脂酰CoA去饱和酶l(stearoyl-CoA desaturase-1，SCD1)mRNA及蛋白表达。结果显示，与Con组相比，Mod组TG、TC、LDL-C水平显著升高，HDL-C水平显著降低(P＜0.01)；肝细胞存在大量脂肪空泡，且肝脏脂质沉积情况明显；TG、FFA含量上升(P<0.01)；SQLE、CA3、SREBP1c、ACC、FASN、SCD1蛋白与mRNA表达升高(P＜0.05或P＜0.01)。与Mod组相比，GPs组TC、TG、LDL-C水平显著降低，HDL-C水平显著升高(P＜0.01)；肝细胞形态趋于正常且脂滴减少，肝脏脂质沉积减轻；TG、FFA含量显著下降(P<0.01)；SQLE、CA3、SREBP1c、ACC、FASN、SCD1蛋白与mRNA表达下降(P＜0.05或P＜0.01)。由此可见，GPs可以通过SQLE/CA3/SREBP1c途径，抑制脂肪酸合成，减少脂质蓄积，从而改善NAFLD。

关键词: 绞股蓝皂苷, SQLE-CA3轴, 脂肪酸合成, 肝脏脂质沉积, 非酒精性脂肪肝病

Abstract:

This study aims to investigate the effect of gypenosides (GPs) on nonalcoholic fatty liver disease (NAFLD) by improving liver lipid deposition,and to explore its potential mechanism.Twelve ApoE-/- mice were randomly divided into model group (Mod) and gypenosides group(GPs),and six C57BL/6J mice were used as blank control (Con) group.Con group was fed with normal diet,and the other groups were fed with high-fat diet for 12 weeks.GPs group was given 2.97 g/(kg·d) by gavage,and Con group and the Mod group were given the same volume of normal saline by gavage for 4 weeks.The levels of triglyceride (TG),total cholesterol (TC),low-density lipoprotein cholesterol (LDL-C),high-density lipoprotein cholesterol (HDL-C) level in mice serum were detected by fully automated biochemical analyzer,hematoxylin-eosin (HE) staining to observe the mice liver pathological morphology,oil red O staining to observe the mice liver lipid deposition,the contents of TG and free fatty acid (FFA) in liver were detected by ELISA.The mRNA and protein expression squalene cyclooxygenase (SQLE),carbonic anhydrase Ⅲ (CA3),sterol regulatory factor binding protein-1c (SREBP1c),acetyl-coa carboxylase (ACC),fatty acid synthase (FASN),stearoyl-CoA desaturase 1 (SCD1) in liver were detected by real-time PCR and Western blot.The results showed that compared with Con,the levels of TC,TG and LDL-C in Mod group were significantly increased,and the level of HDL-C was significantly decreased (P<0.01).There were a large number of fat vacuoles in hepatocytes,and the liver lipid deposition was obvious;the contents of TG and FFA increased (P<0.01).SQLE,CA3,SREBP1c,ACC,FASN,SCD1 protein and mRNA expression increased (P < 0.05 or P < 0.01).Compared with Mod,TG,TC,LDL-C were significantly reduced and HDL-C were significantly increased in GPs group (P<0.01);the morphology of hepatocytes tended to be normal and lipid droplets decreased,liver lipid deposition loss;TG and FFA content decreased significantly (P<0.01);SQLE,CA3,SREBP1c,ACC,FASN and SCD1 proteins and mRNA expression decreased (P < 0.05 or P<0.01).In conclusion,gypenosides can inhibit fatty acid synthesis and reduce lipid accumulation through SQLE/CA3/SREBP1C pathway,thereby improving NAFLD.

Key words: gypenosides, SQLE-CA3 axis, fatty acid synthesis, lipid deposition in liver, nonalcoholic fatty liver disease

中图分类号: R256.49 R285.5

孙小扉, 宋囡, 曹媛, 杨莹, 朱敬轩, 高浩, 王嘉鑫, 贾连群. 基于SQLE/CA3/SREBP1c途径研究绞股蓝皂苷改善非酒精性脂肪肝病的机制[J]. 天然产物研究与开发, 2025, 37(4): 687-693.

SUN Xiao-fei, SONG Nan, CAO Yuan, YANG Ying, ZHU Jing-xuan, GAO Hao, WANG Jia-xin, JIA Lian-qun. Mechanism of gypenoside in improving non-alcoholic fatty liver disease based on SQLE/CA3/SREBP1c pathway[J]. NATURAL PRODUCT RESEARCH AND DEVELOPMENT, 2025, 37(4): 687-693.

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基于SQLE/CA3/SREBP1c途径研究绞股蓝皂苷改善非酒精性脂肪肝病的机制

Mechanism of gypenoside in improving non-alcoholic fatty liver disease based on SQLE/CA3/SREBP1c pathway

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