基于PI3K-AKT-mTOR通路探讨泽曲明山复方对大鼠非酒精性脂肪性肝炎模型的影响  

Effect of Zequ Mingshan Compound Prescription(泽曲明山复方)on Mouse Model of Non-alcoholic Steatohepatitis

作　　者：郑佳连[1] 张艳[2] 卢秉久[2] 张红 韩永辉[4] 付博[1] ZHENG Jialian;ZHANG Yan;LU Bingjiu;ZHANG Hong;HAN Yonghui;FU Bo(Liaoning University of Tradition Chinese Medicine,Shenyang 110847,Liaoning,China;Affiliated Hospital of Liaoning University of Tradition Chinese Medicine,Shenyang 110032,Liaoning,China;Anshan Mental Health Center,Anshan 114001,Liaoning,China;The Sixth Peoples'Hospital of Shenyang,Shenyang 110006,Liaoning,China)

机构地区：[1]辽宁中医药大学,辽宁沈阳110847 [2]辽宁中医药大学附属医院,沈阳辽宁110032 [3]鞍山市精神卫生中心,辽宁鞍山114001 [4]沈阳市第六人民医院,辽宁沈阳110006

出　　处：《中华中医药学刊》2024年第12期117-121,I0041-I0047,共12页Chinese Archives of Traditional Chinese Medicine

基　　金：国家自然科学基金面上项目(82174241);辽宁省自然基金资助计划项目(2019-MS-231)。

摘　　要：目的泽曲明山复方是临床治疗代谢相关性脂肪性肝病(MAFLD)的经验方。研究探讨该经验方对大鼠非酒精性脂肪性肝炎(NASH)模型的影响以及可能的机制。方法Sprague-Dawley大鼠给予胆碱缺乏高脂饲料(CDHFdiet)8周建立NASH模型。随机分为模型组,中药低、高剂量组以及水林佳组;建立模型同时给予对应药物干预。给予胆碱充足高脂饲料(CSHFdiet)作为对照组。观察相应药物对模型大鼠血清生化学、肝脏病理、磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(PKB/AKT)/哺乳动物雷帕霉素靶蛋白(mTOR)通路信号转导通路mRNA、蛋白表达的影响。结果(1)体质量以及肝脏/体质量:5组大鼠体质量差异无统计学意义,模型组大鼠肝脏/体质量显著升高,各干预组大鼠肝脏/体质量不同程度下降,中药高剂量组疗效最为明显。(2)肝功能以及血脂:与对照组相比,模型组大鼠血清肝功能及血脂水平显著升高;各干预组大鼠肝功能以及血脂不同程度降低,其中中药高剂量组疗效最为明显。(3)肝脏病理:模型组大鼠肝脏HE染色可见胞浆内大量脂肪空泡以及炎性细胞浸润;Siriusred染色可见中央静脉大量纤维组织沉积,证实模型成立;各干预组肝脏HE以及Siriusred染色均有不同程度改善,中药高剂量组改善最为明显。(4)对肝组织固醇调节元件结合蛋白1(SREBP-1)、低密度脂蛋白受体(LDLR)mRNA表达的影响:与对照组相比,模型组SREBP-1mRNA表达明显升高;各干预组有不同程度下调,其中中药高剂量组最为明显。与对照组相比,模型组大鼠LDLRmRNA表达明显下降;各干预组表达有不同程度增加,其中中药高剂量组改善最为明显。(5)对肝组织SREBP-1、LDLR蛋白表达的影响:与对照组相比,模型组大鼠肝组织中SREBP-1蛋白染色深,各干预组较模型组染色浅,其中中药组效果更显著。与对照组相比,模型组大鼠肝组织中LDLR蛋白染色浅,各干预组较模型组染色深Objective Zequ Mingshan Compound Prescription(泽曲明山复方)is an empirical formula for the clinical treatment of metabolic associated fatty liver disease(MAFLD).This study explored the impact of this empirical formula on the rat model of non-alcoholic steatohepatitis(NASH)and its possible mechanisms.Method SD rats were given choline deficient high fat diet(CDHF diet)for 8 weeks to establish a NASH model.The rats were randomly divided into model group,low and high dose groups of traditional Chinese medicine and Shuilinjia group.The model was established and the corresponding drug intervention was provided.The choline rich high fat diet(CSHF diet)was as the control group.The effects of corresponding drugs on serum biochemistry,liver pathology,PI3K-AKT-mTOR signaling pathway mRNA and protein expression in model rats were compared.Results(1)Body weight and liver/body weight:There was no statistically significant difference in body weight among the 5 groups.The liver/body weight of the rats of the model group significantly increased,while the liver/body weight of the rats of each intervention group decreased to varying degrees.The high-dose group had the most significant therapeutic effect.(2)Liver function and blood lipids:Compared with those of the control group,the serum levels of alaninetransaminase(ALT),glutamic oxaloacetic transaminase(AST),triglyceride(TG),total cholesterol(TC)and low density lipoprotein cholesterol(LDL-C)of the model group were significantly increased.The liver function and blood lipids of rats in each intervention group decreased to varying degrees,with the high-dose group having the most significant therapeutic effect.(3)Liver pathology:HE staining showed a large number of fat vacuoles and inflammatory cell infiltration in the cytoplasm of the liver of the model group rats.Sirius red staining showed a large amount of fibrous tissue deposition in the central vein,confirming the validity of the model.Each intervention group showed varying degrees of improvement in liver HE and Sirius red

关 键 词：泽曲明山复方 非酒精性脂肪性肝炎 PI3K-AKT-mTOR通路 

分 类 号：R256.4[医药卫生—中医内科学]