Clinical Observation And Related Mechanism Of TCM Intervention In Metabolic Syndrome

BackgroundThe incidence rate of Metabolic Syndrome is not only increasing year by year,but also becoming younger.As a new non-communicable disease,Metabolic Syndrome has become the main health hazard in the world.IR is one of the main features and core link of MetS.Traditional Chinese medicine pays attention to the holistic view and syndrome differentiation treatment,which can reduce the side effects of Western medicine,control body mass and improve insulin resistance,but its specific molecular mechanism is not clear.In recent years,in vivo and in vitro experimental studies have shown that the occurrence of IR is closely related to the obstacle of PI3K/AKT signal pathway.The mechanism of action of many traditional Chinese medicine monomers,compounds or Chinese patent medicines is related to this pathway,which has also become the focus of the molecular mechanism research of traditional Chinese medicine in the prevention and treatment of MetS IR.Chapter I Discussion on TCM syndrome differentiation treatment of Metabolic SyndromeObjective:To discuss the TCM syndrome differentiation and treatment scheme of MetS and summarize the distribution law of TCM syndrome types.Methods:One hundred and sixty-three Mets patients were included in the study and divided into exposure group of 80 cases.The intervention measures were TCM syndrome differentiation combined with basic treatment of Western medicine.There were 83 cases in the non-exposure group.The intervention measures were basic treatment of Western medicine.We recorded the whole process of diagnosis and treatment and observed the balance of baseline indexes(gender,age,weight,waist circumference,etc.)of the two groups.The primary efficacy index of HOMA-IR and secondary efficacy indexes(fasting blood glucose,blood lipid,blood uric acid,blood pressure,etc.)were compared.At the same time,the safety indexes(blood routine,urine routine,stool routine,ECG,liver and kidney function)and adverse events were observed and recorded to discuss the clinical efficacy and safety of TCM syndrome differentiation treatment on Mets patients.SPSS software was used to make statistics and analysis on the frequency,clustering and correlation of traditional Chinese medicine.Result:1.163 patients were included in the study,of which 62.58%were male and 37.42%were female.The age is distributed mainly between 40 and 60 years old.In terms of weight and waist circumference,the Clinical effect of integrated traditional Chinese and Western medicine is better than western medicine.The above results showed that attention should be paid to the male population aged 40-60 diagnosed as metabolic syndrome in clinical practice,which can be treated with integrated traditional Chinese and Western medicine to improve body mass.2.In terms of islet function,HOMA-IR level had a significant downward trend through the treatment,and FINS level did not change significantly.In terms of glucose metabolism,TCM treatment based on syndrome differentiation can reduce blood glucose,and it is better than the western medicine group.In lipid metabolism,blood pressure and blood uric acid,it can improve blood lipid metabolism,correct disorder and reduce uric acid,but it has no significant effect on blood pressure.In the curative effect of TCM,the treatment of integrated traditional Chinese and Western medicine has obvious advantages.There were no obvious abnormalities in related checklist,and no adverse events were reported.According to the above results,TCM treatment based on syndrome differentiation can improve insulin resistance,glucose and lipid metabolism and clinical efficacy.3.By analyzing the prescriptions of traditional Chinese medicine in the first diagnosis,we learned common drugs include bupleurum root,white peony root,tuckahoe,Pinellia ternata,Atractylodes rhizome,Fructus aurantii Immaturus,etc.The four Qi of drugs are mostly warm,peaceful and slightly cold.The five flavors of drugs are mainly sweet,bitter and pungent.The channel tropism of drugs are concentrated in the spleen,liver,stomach,lung,kidney and other viscera.The function of TCM focuses on tonifying deficiency,activating blood circulation and removing blood stasis,clearing away heat,resolving phlegm,promoting water and dampness,regulating Qi,etc.Cluster analysis showed that traditional Chinese medicine mainly focused on resolving phlegm and removing blood stasis,dispersing liver,invigorating Qi and blood.Combined with the association rules,it was found that the chinese medicine for promoting the circulation of Qi and removing dampness,phlegm and blood stasis were mostly used in this study.To test and verify by chinese medicine,we found that many patients can be diagnosed as the syndrome of phlegm and blood stasis and the syndrome of Qi stagnation and dampness obstruction.It also shows that in this study,more patients were diagnosed with the above two syndrome types.Conclusion:1.TCM syndrome differentiation treatment combined with basic Western medicine is safe and effective.It can effectively improve clinical symptoms,correct abnormal glucose and lipid metabolism,reduce body weight,reduce waist circumference,improve insulin resistance,and provide objective basis for clinical treatment of MetS.2.The syndrome of phlegm and blood stasis and Qi stagnation and dampness obstruction are common in MetS.The basic chinese medicine includes bupleurum,white peony,Pinellia ternata,Poria cocos,Atractylodes macrocephala and Fructus aurantii.The basic pathogenesis of this disease is mainly spleen deficiency,with pathological factors such as phlegm dampness,blood stasis and heat toxin.It is a disease of deficiency and excess.The disease is mainly located in spleen and liver,involving stomach,lung and kidney.In terms of four Qi,warm drugs are mainly used in clinical practice,taking into account mild and mild cold.In terms of five flavors,sweet drugs are often used in clinic,taking into account bitter and pungent taste.In clinical practice,deficiency tonifying drugs,blood activating and stasis removing drugs,heat clearing drugs and phlegm resolving drugs are often used.Chapter 2 Effect of Dai Zong Recipe on insulin resistance index and inflammatory factors in patients with Metabolic SyndromeObjective:To evaluate the clinical effect of DZF on IR and inflammatory factors in MetS patients with Phlegm Blood Stasis Syndrome.Methods:Twenty five patients with phlegm and blood stasis syndrome treated with Dai Zong recipe were included.The self-control research method was used to compare the efficacy of TCM syndrome treatment before and after treatment(evaluated according to the improvement degree of phlegm and blood stasis syndrome),islet function(blood glucose,insulin and HOMA-IR),NLRP3 inflammatory body and inflammatory factors.Results:Dai Zong Recipe can significantly reduce the score of TCM syndrome(P<0.01)and improve the clinical symptoms of patients with metabolic syndrome.In terms of islet function,Dai Zong recipe could significantly reduce the fasting blood glucose level,fasting insulin level and HOMA-IR(P<0.01).The results of inflammation level test showed that Dai Zong Recipe could reduce NLRP3,IL-6 and IL-1 in patients with metabolic syndrome β(P<0.05).Based on the above results,Dai Zong recipe has advantages in improving insulin resistance and inflammatory factors in patients with phlegm stasis syndrome.Conclusion:DZF has good clinical effect in the treatment of MetS,which can effectively improve the clinical symptoms of phlegm and blood stasis,reduce blood glucose and regulate insulin resistance,so as to provide basis for DZF in the treatment of MetS.We found that DZF can reduce NLRP3 inflammatory body,IL-6 and IL-1β and other inflammatory factors through its own pre and post control,so as to improve the inflammatory level,and finally achieve the purpose of improving IR.Chapter 3 Effect of Dai Zong Recipe on insulin resistance of IR HepG2 cellsObjective:To discuss the effect of DZF on insulin resistance of IR-HepG2 cells.Methods:The insulin resistance model of human Hepatoma cells(HepG2)was induced by the different concentration of insulin.The serum of DZF was used to intervene successfully modeled cells,record the cell viability and glucose consumption,determine the optimal concentration of DZF,and study the effect of DZF on improving IR.Results:HepG2 cells were treated with insulin for 36 hours.After induction,it was found that the cell viability of the model group decreased and the glucose consumption decreased as a whole,suggesting that insulin can induce insulin resistance in HepG2 cells.Compared with the control group,the serum containing DZF at 15%concentration had significant difference compared with other concentrations(P<0.01),which could increase the activity and glucose consumption of IR-HepG2 cells.The above results showed that the intervention effect of 15%concentration DZF prescription containing serum was the best.Conclusion:DZF can significantly improve the IR of IR-HepG2 cells,increase cell viability and glucose consumption,effectively improve the state of IR-HepG2 cells and promote glucose absorption.Chapter 4 Study on the mechanism of Dai Zong Recipe regulating PI3K/Akt signaling pathway to improve IR-HepG2 cellsObjective:In order to find the possible mechanism of DZF in improving IR-HepG2,the study regulate NLRP3 inflammatory corpuscles based on PI3K/AKT signaling pathway.Methods:IL-6,IL-1β,TNF-α,etc inflammatory factor were detected in control group,model group,DZF group and Metformin group.To explore whether DZF can reduce the inflammatory effect,the experiment set up the expression of proteins such as p-PI3Kp85,p-AKT,p-mTOR,NLRP3,caspase-1 and ASC in PI3K/AKT signaling pathway.The relative expressions of PI3K,AKT,mTOR,ASC,caspase-1 and NLRP3 mRNA in the four groups were observed from the perspective of gene.From the point of cellular level,we had an experiment to verify whether DZF intervenes IR by regulating NLRP3 inflammatory bodies through PI3K/AKT signal pathway.Result:1.The ELISA results showed that the level of TNF-、IL-6、IL-1β in the model group were higher than in the control group the level of IR-HepG2 cells(P<0.01);Compared with the model group,the level of TNF-α、IL-6、IL-1β of IR-HepG2 cells in DZF group decreased significantly in the level of inflammation(P<0.01).The above results showed that Dai Zong recipe can effectively improve the inflammatory state.2.The results of Western Blot showed that the expression of p-PI3Kp85 protein in the model group was higher than that in the control group(P<0.05),and the expression of pAKT and p-mTOR protein were significantly higher than that in the control group(P<0.01).Compared with the model group,the expression of p-PI3Kp85 and p-AKT protein in DZF group decreased significantly(P<0.05),and p-mTOR protein decreased,but the difference was not statistically significant(P>0.05).The expressions of NLRP3,caspase1 and ASC protein in the model group were significantly higher than those in the control group(P<0.01).The expressions of NLRP3,caspase-1 and ASC protein in DZF group and metformin group were significantly lower than those in model group(P<0.01).The above results showed that Dai Zong recipe could reduce the expression of p-PI3Kp85,p-AKT,NLRP3,caspase-1 and ASC related proteins.3.PCR results showed that compared with the control group,the expression of PI3K gene and mTOR gene in the model group was increased(P<0.05),and the expression of AKT gene was not statistically significant(P>0.05).Compared with the model group,the expression of PI3K gene and mTOR gene in DZF group and metformin group decreased(P<0.05),and there was no significant difference in AKT gene expression after intervention(P>0.05).Compared with the control group,the expression of NLRP3 gene,caspase-1 gene and ASC gene in the model group increased significantly(P<0.01).The expressions of NLRP3 gene,caspase-1 gene and ASC gene in DZF group and metformin group were significantly lower than those in model group(P<0.01).The above results showed that Dai Zong recipe could reduce the expression of PI3K gene,mTOR gene,NLRP3 gene,caspase-1 gene and ASC gene.Conclusion:IR-HepG2 cells can stimulate the phosphorylation of PI3K,AKT and mTOR,and enhance the expression of protein and gene in NLRP3 inflammatory body,caspase-1,ASC.DZF can significantly inhibit its phosphorylation,reduce the expression of protein and gene in inflammatory body and the level of inflammatory factors.