Study On The Mechanism Of Compound Fufang Zhenzhu Tiao Zhi Formula Regulating Energy Metabolism Based On Ang Ⅱ-AT1R

Objective:This study use high-fat diet（HFD）fed AT1R-KO mice as the research object,based on the TCM theory of"regulating the liver and activating turbid",exploring the energy metabolism effect of Fufang Zhenzhu Tiaozhi capsule（FTZ）on AngⅡ-AT1R axis blocked obese mice,to find its regulatory mechanism,thus the theoretical research basis of Glucolipid Metabolic Disease（GLMD）should be provided.Methords:After confirming the genotype and blood pressure of the AT1R-KO mice,the AT1R-KO mice（KO）and their litter wild-type mice（WT）were randomly divided into 6 groups according to their body weight after being raised to 16weeks of age:litter wild-type mouse normal diet group（WT+SD）,litter wild-type mouse high-fat diet group（WT+HFD）,litter wild-type mouse high-fat diet with FTZ administration group（WT+HFD+FTZ）,AT1R-KO ordinary diet group（KO+SD）,AT1R-KO high-fat diet group（KO+HFD）,AT1R-KO high-fat diet with FTZ administration group（KO+HFD+FTZ）.Blood parameters such as blood glucose,cholesterol,triglycerides,LDL-C and HDL-C were measured with the corresponding kits in mice.The body fat content of mice was measured noninvasively by nuclear magnetic resonance（NMR）whole body composition analyzer.Oxygen consumption and CO₂exhaled volume were measured by comprehensive experimental animal monitoring system.The central body temperature was measured by thermometer.The pathological characteristics of adipose tissue were observed by pathological staining.Energy metabolism related factors in adipose tissue,including fatty acid oxidation,tricarboxylic acid cycle（TCA）and oxidative phosphorylation（OXPHS）,were detected by RT-PCR instrument.Results:1.In high-fat diet induced obese mice,the oxygen consumption,CO2exhalation and body temperature were reduced,and the energy metabolism was markedly reduced.In addition,the mice had a higher expression of AT1a R m RNA in adipose tissue.2.There were no significant differences in abnormal body weight,food intake,glucose metabolism and lipid metabolism between wild-type mice and AT1R-KO mice.But AT1R-KO mice had an increased daytime oxygen consumption.3.The AT1R-KO mice exhibited a sluggish rate of weight gain,a significantly increased oxygen consumption,a higher mitochondrial DNA copy number of adipocytes,and showed an increased expression of m RNA related to energy metabolism,an increased level of PGC-1αand p-AMPK protein.In addition,the total fat content and the body fat rate was decreased.4.AT1R-KO mice and the litter wild type mice similarly showed a sluggish rate of weight gain,and had some increased results in total oxygen consumption and expression of m RNA related to energy metabolism,the level of protein PGC-1αand p-AMPK.The total fat content and the body fat rate were both decreased.However,there were no significant differences in glucose tolerance and daytime oxygen consumption in AT1R-KO miceConclusion:1.AT1R mRNA expression is associated with energy metabolism,and AT1R knockout could promote energy metabolism.2.The mechanism of Ang Ⅱ-AT1R in regulating energy metabolism is related to the activation of AMPK/PGC-1αsignaling pathway.3.The Ang Ⅱ-AT1R axis mediates the regulating effect of FTZ in improving the imbalance of energy metabolism caused by high-fat diet.