| This paper was divided into three parts:literature review,clinical research and animal experimental research.The first part described Metabolic Syndrome(MetS),gut microbiota and the relationship between them from the perspective of Western medicine and traditional Chinese medicine.The second part studied the pathogenesis and potential risk factors of MetS complication and distribution of TCM syndromes.In the animal experimental study,the mechanism of MetS caused by diet-induced gut microbiota disorder and the regulatory effect of Chaiqi decoction on this mechanism were discussed.1.Literature ReviewThis study collected and sorted out the Chinese and English literatures on Pubmed and Cnki in the past ten years,and then summarized the epidemiology,etiology,diagnosis and treatment of MetS and its complication,as well as the research progress of the relationship between gut microbiota and MetS,and finally summarized the understanding of MetS in traditional Chinese medicine.2.Clinical researchObjective:To study the pathogenesis and potential risk factors of MetS complication and distribution of TCM syndromes.Methods:This paper collected the age,weight,height,fasting blood glucose,blood lipid,blood pressure,fasting insulin,fasting C-peptide,HbAlc and complications of the patients with MetS who were admitted in the Department of Endocrinology,Dongfang Hospital Beijing University of Chinese Medicine from September 2018 to August 2019.Result:There were 259 males and 347 females with MetS,with the ratio of male to female 1:1.3.The age of patients with MetS is between 20 and 94 years old,patients aged 50 to 69 years old being the highest(57.9%).Obesity(BMI>25kg/m2)was negatively correlated with age.Among people under 80 years old,poor control of blood glucose(HbA1c>8%)and poor control of blood lipids were negatively correlated with age,while hypertension was positively correlated with age.Liver stagnation and spleen deficiency syndrome accounted for the highest proportion in all the population,and was negatively correlated with age.The incidence of CKD is high in MetS patients with deficiency of spleen and kidney.The incidence of MetS complication from high to low was:carotid atherosclerosis(CAS)(77.9%),low extremity atherosclerosis disease(LEASD)(73.4%),metabolic dysfunction-associated fatty liver disease(MAFLD)(71.1%),coronary atherosclerotic heart disease(CHD)(33.0%),cerebralvascular accident(CVA)(28.4%),chronic kidney diseases(CKD)(8.6%).The risk factors of CAS were hypertension and age being equal and older than 40 years old.The risk factors of LEASD were male,hypertension and age being equal and older than 60 years old.The risk factors of MAFLD were BMI being equal and greater than 25kg/m2 and TG over 1.7 mmol CHD.The risk factors of CVA were female,hypertension and age being equal and older than 80 years old.The risk factors of CKD were hypertension,age being equal and older than 80 years old and fasting C-peptide over 4.4ng/mL.Conclusion:50-69 years old is the age with high incidence of MetS.Young patients with MetS generally lose control of blood sugar,blood lipids and body weight.Liver stagnation and spleen deficiency are the main pathogenesis of METS,and are more common in the early stage of the disease.Among the complication of MetS,the incidence of CAS,LEASD and MAFLD was the highest,CHD and CVA took the second place,and CKD was the lowest.Age and hypertension are common risk factors for CAS,LEASD,CHD,CVA and CKD.Age≥40 is a risk factor for CAS,age≥60 is a risk factor for CHD and LEASD,and age>80 is a risk factor for CVA and CKD.Gender is a special risk factor for LEASD and CVA.Males are more likely to suffer from LEASD,and females are more likely to suffer from CVA.Fasting C-peptide over 4.4ng/mL is a special risk factor for CKD.Obesity and high triglycerides are risk factors for MAFLD.3.Experiment researchObjective:To study the mechanism of MetS caused by diet-induced gut microbiota disorder and the regulatory effect of Chaiqi decoction on this mechanism.Methods:The MetS model was established by feeding SD rats with high-fat,high-sugar and high-salt diet.After 8 weeks of successful modeling,drug intervention was given.At the end of the 16th week of the experiment,body weight,fat weight and blood pressure were measured,and then the samples were killed.Blood glucose,blood lipids,as well as LPS,IL-6 and TNF-α in serum,expression of NF-κB p65,TLR4 and MyD88 in adipose tissue,macrophage infiltration in adipose tissue were detected,and gut microbiota were detected by 16SrRNA high-throughput sequencing.Result:Compared with the blank control group,traditional Chinese medicine group and diet intervention group,the blood glucose,blood lipid,blood pressure and body weight in the model group increased significantly,and the contents of LPS,IL-6 and TNF-α in serum increased,the expression of NF-κB p65,TLR4 and MyD88 in adipose tissue increased,and the infiltration of macrophages in adipose tissue was obvious.Chaiqi decoction and caloric restriction both can effectively reverse the above-mentioned indexes and pathological changes,arid the effect of Chaiqi decoction is stronger than caloric restriction.Compared with the blank control group,traditional Chinese medicine group and diet intervention group,the changes in the model group were as follows.The species composition and function of gut microbiota changed,the ratio of Firmicutes/Bacteroides increased,and the proportion of gram-negative bacteria increased.The relative abundance of OTU504,OTU552 and OTU485 increased,which belonged to Blautia,Turicibacter and spirillaceae family,and the relative abundance of OTU276 decreased,which belonged to Lactobacillus Ruminococcaceae and Clostridiaceae 1 family.The migration and apoptosis of gut microbiota were active,the host’s ability of absorption and utilization of nutrients in food decreased,and the relative proportion of enteric pathogenic bacteria increased.Both Chaiqi decoction and caloric restriction can effectively reverse the changes of species composition and function of gut microbiota,and the effect of Chaiqi decoction in improving the abundance of Ruminococcaceae is significantly stronger than others.Conclusion:Chaiqi decoction and caloric restriction could effectively improve the body weight,blood pressure,blood lipid and blood glucose of MetS rats,and the weight loss and antihypertensive effect of Chaiqi decoction was better than that of caloric restriction.The relative abundance of gram-negative bacteria in gut microbiota increased,the release of LPS increased,which led to metabolic endotoxemia through signal transduction of LPS-TLR4/MyD88-NF-κB,which may be the main mechanism of MetS caused by diet-induced gut microbiota disorder.At the same time,the change of species composition of gut microbiota,the migration and apoptosis of gut microbiota,the decrease of the host’s ability of absorption and utilization of nutrients in food and the increase of the proportion of enteric pathogenic bacteria may be the potential mechanisms of the pathogenesis of MetS.Chaiqi decoction and caloric restriction treat MetS mainly by reducing the relative abundance of gram-negative bacteria in gut microbiota and inhibiting the release of LPS,thus inhibiting the signal transduction of LPS-TLR4-MyD88-NF-κB and reducing metabolic endotoxemia.The effect of Chaiqi decoction was better than caloric restriction.At the same time,both ways could also reverse the changes of species composition of MetS gut microbiota,reduce the abnormal apoptosis and migration of bacteria,enhance the ability of host to absorb and utilize nutrients,and reduce the relative proportion of enteric pathogenic bacteria to improve the metabolic disorder of MetS.And the increase of the abundance of Ruminococcaceae may be an important potential mechanism of Chaiqi decoction in the treatment of metabolic syndrome. |
PDF Full Text Request