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

作　　者：孙小扉 宋囡[1] 曹媛[1] 杨莹 朱敬轩 高浩 王嘉鑫 贾连群[1] 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)

机构地区：[1]辽宁中医药大学,沈阳110847

出　　处：《天然产物研究与开发》2025年第4期687-693,共7页Natural Product Research and Development

基　　金：国家自然科学基金(82374423,82074145)。

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 anhydraseⅢ,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。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 anhydraseⅢ(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<

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 

分 类 号：R256.49[医药卫生—中医内科学] R285.5[医药卫生—中医学]