Glycolipid Metabolism Research In Different Age Mice With LC-MS And Effect Of FTZ Intervention

Background:The aging process is accompanied by the changes of physiological function and organ degeneration.The liver is an important organ with high metabolic rate.With aging,the telomere of the liver is shortened,the ability of glucose and lipid metabolism is decreased,et al.At the same time,accompanied by inflammation,liver aging can increase the risk of liver disease and accelerate the aging of the body.FTZ,as a prescription for regulating liver function,is under the guidance of the theory of regulating liver opening and armature turbid.In previous studies,the prescription has the effects of lowering blood sugar,reducing lipid,anti-inflammation,anti-aging,et al.Therefore,the pharmacodynamics and mechanism of FTZ on the target organs during liver aging were investigated.Objective:The characteristics of glucose and lipid metabolism in C57BL/6J model of natural aging mice were analyzed systematically,and the pathological characteristics of liver tissues during natural aging were determined.The aging of liver was researched from the telomerase activity,serum and liver metabolomics,and the expression of inflammatory factors.and then explorring the mechanisms of FTZ anti-aging from above parts.Methods:1 The C57BL/6J mice were used to established the natural aging model.they were randomly divided into seven groups: March model group(M3),September model group(M9),14 month model group(M14),20 month model group(M20),and 20 month FTZ group(F20),F20 groups was administration of FTZ for 12 weeks.The anti-aging effect of compound FTZ was evaluated by testing Biochemical indexes,telomerase activity and pathology of liver tissue.2 Endogenous difference metabolism of serum and liver in aging animal model was researched by LC-MS,and the regulating effect of FTZ recipe on different metabolites in serum and liver tissue was discussed.3 The mechanism of inflammation and senescence in aging mice was researched by determining the expression of IL-6\TNF-?\AP-1 and COX-2 in liver tissue using the RT-PCR.Results: 1 Pharmacodynamics(1)The ability of autonomous activity and fatigue latency decreased with the aging of mice,but after the intervention of FTZ,the ability of autonomous activity and the latent time of fatigue increased significantly.(2)There was a significant difference in TC,TG,LDL-C,HDL-C,FFA.After administration of FTZ,the TC,TG,LDL-C,HDL-C,FFA were significantly improved.The result showed that there was a significant difference between the two groups among the senescence.(3)With aging,telomerase activity in liver tissue were decreased;AST and ALT,the liver function index,were increased significantly;liver structure was damaged,the level of liver function index AST,ALT was significantly decreased and liver structure was improved in FTZ group.2 Metabolism results(1)The mass spectrometry of serum metabonomics were determined by the least squares discriminant analysis(OPLS-DA).The results showed that M3,M9,M14,M20,F20 could be separated from each other significantly.34 markers were identified based on HMDB and other databases,mainly related to amino acid metabolism,lipid metabolism,glucose metabolism,bile acid metabolism and arachidonic acid metabolism.(2)The metabonomics of liver were analyzed by OPLS-DA,The results showed that M3,M9,M14,M20,F20 could be distinguished from other groups.In combination with HMDB database,44 markers were found and mainly related to amino acid metabolism,lipid metabolism,glucose metabolism,bile acid metabolism and arachidonic acid metabolism.Mechanism research:The relative expression of IL-6\TNF-?\AP-1 and COX-2 in liver tissue of natural aging model mice was significantly increased with the increase of age.The relative expression of IL-6\TNF-?\AP-1 and COX-2 decreased significantly after the intervention of FTZ.Conclusion:With the increase of age,mice have behavioral disorders,disorder of glucose and lipid metabolism,aging of liver with inflammation.Zhenzhu Tiaozhi recipe has the effects of regulating glucose and lipid metabolism,improving liver structure and function,and anti-aging in natural aging model mice.The mechanism may be related to the improvement of liver inflammation.