茯苓多糖通过调控Akt/mTOR/SREBP-1c信号通路对非酒精性脂肪性肝病小鼠的改善作用  

Effects of Poria coco s polysaccharides on improving mouse nonalcoholic fatty liver disease via regulation of Akt/mTOR/SREBP-1c signaling pathway

作　　者：黄诗瑶 孔亮[2] 王佳华 王莉艳 孙朝渭 刘鑫程 董禹何 谷丽艳[3] HUANG Shi-yao;KONG Liang;WANG Jia-hua;WANG Li-yan;SUN Chao-wei;LIU Xin-cheng;DONG Yu-he;GU Li-yan(College of Traditional Chinese Medicine,Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China;School of Pharmacy,Liaoning University of Traditional Chinese Medicine,Dalian 116600,China;Ministry of Education Key Laboratory for Brief Theory of Viscera and Their Manifestations and Application of Traditional Chinese Medicine,Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China)

机构地区：[1]辽宁中医药大学中医学院,辽宁沈阳110847 [2]辽宁中医药大学药学院,辽宁大连116600 [3]辽宁中医药大学中医脏象理论及应用教育部重点实验室,辽宁沈阳110847

出　　处：《中成药》2025年第1期58-65,共8页Chinese Traditional Patent Medicine

基　　金：国家自然科学基金资助项目(82204629);辽宁省科技厅博士启动基金(2022-BS-197);辽宁中医药大学大学生创新创业训练计划项目(X202310162044)。

摘　　要：目的探讨茯苓多糖对非酒精性脂肪性肝病(NAFLD)小鼠的改善作用。方法48只C57BL/6小鼠随机分为空白组、模型组、辛伐他汀组(4 mg/kg)和茯苓多糖高、中、低剂量组(200、100、50 mg/kg),每组8只,采用高脂高胆固醇饮食饲喂16周复制NAFLD模型,分别灌胃给予相应药物,连续8周。观察各组小鼠体质量、肝脏系数,检测肝组织游离脂肪酸(FFA)水平,血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、γ-谷氨酰转移酶(γ-GT)、丙二醛(MDA)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)水平和超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性;HE染色、NAFLD活动评分(NAS)及油红O染色观察肝组织病理变化、脂质沉积情况;Western blot法检测肝组织Akt、mTOR、p-Akt、p-mTOR、SREBP-1c蛋白表达。结果与空白组比较,模型组小鼠体质量、肝脏系数、肝组织FFA水平,以及血清TC、TG、LDL-C、AST、ALT、γ-GT、MDA、IL-1β、TNF-α水平均升高(P<0.05,P<0.01),HDL-C水平及SOD、GSH-Px活性降低(P<0.05,P<0.01),肝组织存在明显的病理损伤,NAS评分升高(P<0.01),脂质沉积面积增加(P<0.01),肝组织p-Akt、p-mTOR、SREBP-1c蛋白表达升高(P<0.05);与模型组比较,辛伐他汀组和茯苓多糖高、中剂量组小鼠体质量、肝脏系数、肝组织FFA水平、血清TC、TG、LDL-C、AST、ALT、γ-GT、MDA、IL-1β、TNF-α水平降低(P<0.05,P<0.01),HDL-C水平及SOD、GSH-Px活性升高(P<0.05,P<0.01),肝组织病理损伤减轻,NAS评分降低(P<0.05,P<0.01),脂质沉积面积减少(P<0.05,P<0.01),肝组织p-Akt、p-mTOR、SREBP-1c蛋白表达降低(P<0.05)。结论茯苓多糖能改善小鼠非酒精性脂肪性肝病,其作用机制可能与抑制Akt/mTOR/SREBP-1c信号通路、逆转脂质异常代谢有关。AIM To investigate the improvement effects of Poria cocos polysaccharides(PCPs)on mouse nonalcoholic fatty liver disease(NAFLD).METHODS Forty-eight C57BL/6 mice were randomly divided into the blank group,the model group,the simvastatin group(4 mg/kg)and the high,medium and low dose PCPs groups(200,100 and 50 mg/kg),with 8 mice in each group.The NAFLD model was reproduced by 16 weeks feeding of high-fat and high-cholesterol diet,followed by 8 weeks administration of corresponding drug by gavage.The mice had their body mass and liver coefficient assessed;their levels of hepatic free fatty acid(FFA),and serum total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),aspartate aminotransferase(AST),alanine aminotransferase(ALT),γ-glutamyltransferase(γ-GT)and malondialdehyde(MDA)detected;their hepatic pathological changes and lipid deposition observed using HE staining,NAFLD activity score(NAS)and oil red O staining;and their hepatic protein expressions of Akt,mTOR,p-Akt,p-mTOR and SREBP-1c detected by Western blot.RESULTS Compared with the blank group,the model group demonstrated all increased body weight,liver coefficient,hepatic FFA level,and serum TC,TG,LDL-C,AST,ALT,γ-GT,MDA,IL-1βand TNF-αlevels(P<0.05,P<0.01);decreased HDL-C level and activities of SOD and GSH-Px(P<0.05,P<0.01);more obvious hepatic pathological damage as revealed by increased NAS score(P<0.01)and increased lipid deposition area(P<0.01).Compared with the model group,the groups intervened with high or medium dose PCPs,or simvastatin displayed decreased body weight,liver coefficient,hepatic FFA level,and serum TC,TG,LDL-C,AST,ALT,γ-GT,MDA,IL-1βand TNF-αlevels(P<0.05,P<0.01);increased HDL-C level and SOD,GSH-Px activities(P<0.05,P<0.01);decreased hepatic pathological damage as revealed by the decreased NAS score and lipid deposition area(P<0.05,P<0.01);and decreased hepatic protein expressions of p-Akt,p-mTOR and SREBP-1c protein(P<0.05)as well.CONCLUSION PCPs can improve mo

关 键 词：茯苓多糖 非酒精性脂肪性肝病(NAFLD) 脂质代谢 Akt/mTOR/SREBP-1c信号通路 

分 类 号：R285.5[医药卫生—中药学]