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The Pharmacodynamics And Metabonomics Research Of Five Kinds Of "surgery" Type Invigorating The Spleen And Anti-rheumatic

Posted on:2021-02-11Degree:MasterType:Thesis
Country:ChinaCandidate:B X ZhangFull Text:PDF
GTID:2434330614457731Subject:Pharmacy
Abstract/Summary:PDF Full Text Request
Purpose:Based on the study of A.coreana,A.japonica,A.chinensis,A.lancea and A.macrocephala,spleen invigorating and anti rheumatism,the difference of efficacy among the five medicinal species in Atractylodes DC.was clarified.The biomarkers related to spleen qi deficiency,spleen yang deficiency and rheumatoid arthritis in rats' plasma were found out by metabonomics technology,and the differences of the effects of five medicinal species in Atractylodes DC.on the biomarkers were analyzed.From the perspective of pharmacodynamics and metabonomics,the mechanism of spleen strengthening and anti rheumatism of five medicinal species in Atractylodes DC.was explained,which provided scientific basis for the rational application of A.japonica and A.coreana.Material and method:1.SD rats were randomly divided into control group,model group,positive drug(Shenling Baizhu powder)group,A.coreana group,A.japonica group,A.lancea group,A.chinensis group and A.macrocephala group.The spleen qi deficiency model of rats was established by improper diet and exhausted swimming.After molding,besides the control group and the model group,the other six groups were treated with Shenling Baizhu powder,A.coreana,A.japonica,A.lancea,A.chinensis and A.macrocephala suspension respectively.The changes of body weight,anal temperature,immune organ coefficient and behavior state of rats before and after modling were investigated.The levels of IL-6,TNF-?,IFN-? and Ig G related to gastrointestinal inflammation,MTL,GAS,AMS and SDH related to digestive system,SOD,GSH-PX,CAT and MDA related to antioxidant enzyme systemin in each group rats plasma were determined by enzyme-linked immunosorbent assay(ELISA).The total ions chromatogram of rat plasma was established by UPLC-Q-TOF-MS,then the metabolic spectrum of rat plasma was collected.Combined with OPLS-DA analysismethod to find the related biomarkers of spleen qi deficiency rats,summarize the metabolic pathway,and compare the regulatory effect of five medicinal species in Atractylodes DC.on spleen qi deficiency related biomarkers.2.SD rats were randomly divided into control group,model group,positive drug(Ping Wei San)group,A.coreana group,A.japonica group,A.lancea group,A.chinensis group and A.macrocephala group.The spleen yang deficiency model of rats was established by diet disorder,excessive fatigue and diarrhea due to bitter cold.After molding,besides the control group and the model group,the other six groups were treated with Ping Wei San,A.coreana,A.japonica,A.lancea,A.chinensis and A.macrocephala suspension respectively.The changes of body weight,anal temperature,immune organ coefficient and behavior state of rats before and after molding were investigated.The content of SS,AMS,D-xylose,MTL,GAS and TRY related to digestive system,Ig G,IL-6 and TNF-? related to gastrointestinal inflammation,Na+-K+-ATPase,AQP3 and AQP8 related to intestinal water metabolism in each group rats plasma were determined by ELISA.The total ions chromatogram of rat plasma was established by UPLC-Q-TOF-MS,then the metabolic spectrum of rat plasma was collected.Combined with OPLS-DA analysis method to find the related biomarkers of spleen yang deficiency rats,summarize the metabolic pathway,and compare the regulatory effect of five medicinal species in Atractylodes DC.on spleen yang deficiency related biomarkers.3.SD rats were randomly divided into control group,model group,methotrexate group,tripterygium glycosides group,A.coreana group,A.japonica group,A.lancea group,A.chinensis group and A.macrocephala group.The rheumatoid arthritis model was established with Freund's complete adjuvant.After molding,besides the control group and the model group,the other seven groups were treated with methotrexate,tripterygium glycosides,A.coreana,A.japonica,A.lancea,A.chinensis and A.macrocephala suspension respectively.The changes of body weight,swelling degree of paws,arthritis index and immune organ coefficient of rats in each group were investigated.The contents of IL-6,TNF-?,RF,anti-CCP,IL-1 ?,NF-? B,IL-10 and PGE2 in each group were determined by ELISA,and the differences among thegroups were compared.The total ions chromatogram of rat plasma was established by UPLC-Q-TOF-MS,then the metabolic spectrum of rat plasma was collected.Combined with OPLS-DA analysis method to find the related biomarkers of rheumatoid arthritis rats,summarize the metabolic pathway,and compare the regulatory effect of five medicinal species in Atractylodes DC.on rheumatoid arthritis related biomarkers.Results:1.Five medicinal species in Atractylodes DC.can reduce the content of Ig G,TNF-?,IL-6 and MDA,and increase the content of IFN-?,AMS,MTL,GAS,SDH,GSH-Px,CAT and SOD.In the aspect of eliminating digestive tract inflammation,A.chinensis and A.lancea have better effect.In the aspect of regulating digestive system,A.japonica and A.lancea have better and similar effect.In the aspect of regulating the system of antioxidant enzymes,A.coreana and A.chinensis have better and similar effects.After the spleen qi deficiency in rats,the metabolism of small substances such as arachidonic acid,uracil and cholic acid was disordered,which directly affected metabolic pathways such as glycerol phospholipid metabolism,arachidonic acid metabolism and primary bile acid biosynthesis,resulting the symptoms of insufficient energy supply,decreased antioxidant activity and immune function in the body of rats.Most of the metabolic pathways tend to be control group after oral administration of five medicinal species in Atractylodes DC..Among them,A.coreana and A.chinensis have better and similar intervention callback effect in arachidonic acid metabolism and primary bile acid biosynthesis,while A.macrocephala has stronger intervention callback effect on taurocholic acid biomarkers.The mechanism of action of A.japonica and A.lancea is similar,which plays a better role in the metabolism of glycerol phospholipid metabolism,steroid biosynthesis and pyrimidine metabolism.2.Five medicinal species in Atractylodes DC.can reduce the content of TNF-?,IL-6,Ig G and SS,and increase the content of AMS,D-xylose,MTL,GAS,TRY,AQP3,AQP8 and Na+-K+-ATPase.In the aspect of regulating the absorption and secretion of digestive system,A.coreana and A.chinensis have better and similar regulating effects.In the aspect of eliminating digestive tract inflammation,A.japonica and A.lancea have better and similar regulatory effects.In the aspect of regulating water metabolism,A.chinensis,A.coreana and A.macrocephala are better than the other two.After the spleen yang deficiency in rats,the metabolism of small substances such as linoleic acid,arachidonic acid and vitamin A was disordered,which directly affected metabolic pathways such as linoleic acid metabolism,arachidonic acid metabolism and retinol metabolism,resulting the symptoms of insufficient energy supply,decreased immune function,diarrhea and loose stools in the body of rats.Most of the metabolic pathways tend to be control group after oral administration of five medicinal species in Atractylodes DC..Among them,A.coreana and A.chinensis have better and similar effects on the intervention of retinol metabolism and glycerol phospholipid metabolism.Similar to A.japonica,A.lancea has a better effect on galactose metabolism,while A.macrocephala has a stronger intervention and callback effect on biomarkers that play the role of immune regulation.3.Five medicinal species in Atractylodes DC.can reduce the levels of IL-6,IL-1 ?,PGE2 and NF-?B in the plasma of adjuvant arthritis rats in varying degrees,among which the regulation of A.macrocephala is relatively weak.A.chinensis,A.lancea,A.coreana and A.japonica can significantly reduce the content of TNF-?,in which A.japonica and A.lancea have better and similar regulatory effects.A.chinensis and A.coreana can significantly reduce the content of RF in arthritis rats.A.coreana,A.lancea and A.japonica can significantly reduce the anti-CCP level,that is,the regulatory effect of A.coreana and A.chinensis is similar.The metabolic disorder of11-deoxycortisol,taurocholate and other small molecules in the body of rats with rheumatoid arthritis directly affects the metabolic pathways of primary bile acid biosynthesis and steroid hormone biosynthesis,leading to the decline of immune function and other symptoms.Most of the metabolic pathways tend to be control group after oral administration of five medicinal species in Atractylodes DC..Among them,the regulating effect of A.coreana and A.chinensis is similar,while that of A.japonica and A.lancea are similar.A.macrocephala had little effect of intervention.Conclusion:1.Five medicinal species in Atractylodes DC.have certain therapeutic effect on rats with spleen qi deficiency.Among them,the therapeutic mechanism and of A.coreana and A.chinensis is basically the same as the intervention of biomarkers.However,the therapeutic mechanism and the intervention of biomarkers of A.japonica is more similar to that of A.lancea.2.Five medicinal species in Atractylodes DC.have certain therapeutic effect on the rats with spleen yang deficiency.The therapeutic mechanism of A.coreana and its intervention and callback effect on biomarkers are basically the same as that of A.chinensis,while the therapeutic mechanism of A.japonica and its intervention and callback effect on biomarkers are more similar to that of A.lancea,and the therapeutic effect is relatively weak.3.A.chinensis,A.lancea,A.coreana and A.japonica all have certain therapeutic effects on rats with rheumatoid arthritis.The therapeutic effect of A.coreana is the best and its intervention and callback effect on biomarkers is closer to A.chinensis,while the therapeutic mechanism and intervention and callback effect on biomarkers of A.japonica are closer to A.lancea.
Keywords/Search Tags:Atractylodis Rhizoma, Atractylodis Macrocephalae Rhizoma, Spleen Qi deficiency, Spleen Yang deficiency, Rheumatoid arthritis, Metabonomics, UPLC-Q-TOF-MS
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