乙肝肝硬化肝胆湿热及肝肾阴虚证物质基础研究  

Study of Material base on Hepatitis B Cirrhosis of Gan Dan Shi Re Pattern and Gan Shen Yin Xu Pattern

作　　者：赵超群[1] 蔡虹[2] 陈龙 姚伟丽 周群 朱会明 高悦 刘毓 刘平[1,3] 苟小军 张华[1] Zhao Chaoqun;Cai Hong;Chen Long;Yao Weili;Zhou Qun;Zhu Huiming;Gao Yue;Liu Yu;Liu Ping;Gou Xiaojun;Zhang Hua(Institute of Liver Disease,Shuguang Hospital,Shanghai University of Traditional,Chinese Medicine,Key Laboratory of Clinical Chinese Medicine,Key Laboratory of Liver and Kidney Diseases of Ministry of Education,Shanghai,201203,China;Xiamen Hospital,Beijing University of Traditional Chinese Medicine,Fujian,361000,China;E-Institute of Shanghai Municipal Education Commission,Shanghai,201203,China;Baoshan District Hospital of Integrated Traditional Chinese and Western Medicine of Shanghai,Shanghai,201999,China)

机构地区：[1]上海中医药大学附属曙光医院,上海中医药大学肝病研究所,上海市中医临床重点实验室肝肾病证教育部重点实验室,上海201203 [2]北京中医药大学附属厦门医院,福建361000 [3]上海中医药大学上海高校中医内科学E-研究院,上海201203 [4]上海市宝山区中西医结合医院,上海201999

出　　处：《世界科学技术-中医药现代化》2020年第4期1121-1131,共11页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：国家自然科学基金资助面上项目(81673849):慢性乙型肝炎及非酒精性脂肪性肝病“湿热证”的代谢网络研究,负责人:张华

摘　　要：目的运用代谢组学技术分析乙肝肝硬化患者肝肾阴虚及肝胆湿热两种典型证候(同病异证)的血清差异代谢产物及其代谢通路,探寻虚、实两种典型证候的内在物质基础,以期从代谢水平上为中医证候分类提供客观依据。方法对符合纳入标准的111例不同证候的乙肝肝硬化患者(肝胆湿热证40例,肝肾阴虚证41例,隐证(无证可辨)者30例)中医症状及体征进行描述性分析,发现两种不同证型的临床信息分布规律及证候特征;采用气相色谱-飞行时间质谱联用(GC-TOF/MS)技术对乙肝肝硬化患者,以及与之相匹配的60例健康人的血清样本进行检测,经非监督的主成分分析(Principal Components Analysis,PCA)、有监督的偏最小二乘判别分析(Partial Least Square Discriminant Analysis,PLS-DA)及监督的正交偏最小二乘法(Orthogonal Partial Least SquareDiscriminant Analysis,OPLS-DA)分析,找出与乙肝肝硬化疾病本身及其两种典型证候相关的差异性物质;运用MetaboAnalyst 3.0数据库,寻找并解析肝胆湿热及肝肾阴虚虚实两种证候间差异性物质的相关代谢通路。结果①肝胆湿热证中出现频率较高(50%以上)的症状为小便色黄,口干,口苦,口臭或有异味等。肝肾阴虚证中出现频率较高的症状为口干、腰酸、乏力、腿软等。两证共见症/征为口干、尿黄、易怒、舌红;②各组间丙氨酸氨基转移酶(Alanine Aminotransferase,ALT)数值无统计学差异(P>0.05);与健康组比较,隐证组中白蛋白(Albumin,ALB),肝胆湿热证中总胆红素(Total Bilirubin,TBil)、直接胆红素(Direct Bilirubin,DBil)、谷草转氨酶(Aspartate Transaminase,AST)、碱性磷酸酶(Alkaline Phosphatase,ALP)、谷氨酰转肽酶(Gamma-Glutamyl Transpeptidase,GGT)、总胆汁酸(Total Biliary Acid,TBA)及ALB,肝肾阴虚证TBil、ALP、GGT、TBA、ALB值差异均有统计学意义(P<0.05);与隐证比较,肝胆湿热证TBil、DBil、AST、ALP、TBA、ALB,肝肾阴虚证TBA、ALB差�Objective The serum differential metabolites and metabolic pathways of two typical syndromes of Gan Dan Shi Re Pattern(GDSR)and Gan Shen Yin Xu Pattern(GSYX)in patients with hepatitis B cirrhosis(same disease and different patterns)were analyzed by metabonomics,and the intrinsic material basis of two typical syndromes were explored in order to provide an objective basis for the classification of TCM patterns from the metabolic level.Methods For 111 patients with hepatitis B cirrhosis in accordance with the inclusion criteria(40 patients with GDSR,41 with GSYX,30 Latent Pattern(LP,not-obvious characters),the descriptive analysis was performed to find out the clinical information distribution and syndrome characteristics of two different syndrome types.Then serum samples from the patients with hepatitis B cirrhosis and 60 healthy persons matched with patients were tested based on gas chromatography time of flight coupled with mass spectrometry technique(GC-TOF/MS)to identify the different substances of diseases and two typical patterns.Furthermore,the related metabolic pathway was founded and analyzed by the MetaboAnalyst3.0 database.Results(1)In this study,the symptoms of high frequency(50%or more)in GDSR were found to be yellow urine,dry mouth,bitter mouth,bad breath or odor,and so on.The symptoms of higher frequency of GSYX were dry mouth,backache,fatigue,and soft legs,etc.through descriptive analysis.The common symptoms/signs of two patterns were dry mouth,yellow urine,irritability,red tongue.(2)There was no significant difference in alanine aminotransferase(ALT)between the groups(P>0.05).Compared with the healthy group,there were statistically significant differences in ALB,TBIL,DBIL,AST,ALP in LP,TBIL,DBIL,AST,ALP,GGT,TBA and ALB in GDSR,TBIL,ALP,GGT,TBA and ALB in GSYX(P<0.05).Compared with the LP,there were statistically significant differences in TBIL,DBIL,AST,ALP,TBA and ALB in GDSR,TBA and ALB in GSYX.There were significant differences in TBIL and DBIL between GDSR and GSYX(P<0.05).(3)There was a good di

关 键 词：乙肝肝硬化 同病异证 代谢组学 物质基础 

分 类 号：R241[医药卫生—中医诊断学]