Research On Biomarkers Of Phlegm Dampness Syndrome Of Nonalcoholic Fatty Liver Based On Lipomics

Objective: firstly,through the analysis of the literature on the clinical treatment of nonalcoholic fatty liver disease(NAFLD)in traditional Chinese medicine,the syndrome type and medication rules were obtained,and then based on the literature analysis,the lipid biomarkers of NAFLD phlegm dampness syndrome were explored from the lipidomics level,in order to find new therapeutic targets of NAFLD phlegm dampness syndrome,and provide a new basis for the diagnosis and prevention of NAFLD phlegm dampness syndrome.Methods: firstly,the literature search of clinical research on traditional Chinese medicine treatment of NAFLD was carried out in the database,and the obtained literature was input and removed according to the set inclusion and exclusion criteria.After the integration of the literature,the relevant information of syndrome types,prescriptions,traditional Chinese medicine and other related information was selected for standardized input to generate the original database.After sorting and screening according to the standard format,it was imported into the traditional Chinese Medicine Inheritance computing platform(tcmics V3.0)software to analyze the syndrome types Analysis of medication rules.Lipidomics study NAFLD rat model with phlegm dampness syndrome was made by highfat feed induction method,and the general situation of the rats was recorded.After successful modeling,the rats were sacrificed to obtain the samples to be tested,the blood samples were tested for biochemical indicators,the liver tissues were observed pathologically,and the lipidomics samples to be tested were obtained.Liquid chromatography-mass spectrometry(LC-MS)analysis technology was used to collect the information of lipid metabolites in the liver of rats in the normal group and NAFLD phlegm dampness syndrome group,and to search for differential lipid biomarkers closely related to NAFLD phlegm dampness syndrome.Results: through the analysis of 246 literatures that met the screening conditions,it can be seen that the main NAFLD syndromes were phlegm dampness syndrome,blood stasis syndrome,liver stagnation and spleen deficiency syndrome,and damp heat syndrome,among which phlegm dampness syndrome was particularly prominent,accounting for37.04% of many syndrome types;In the statistics of drug frequency,hawthorn(6.59%),Alisma orientalis(5.85%),Salvia miltiorrhiza(5.59%),Poria Cocos(4.55%),bupleurum(4.43%)were the first.The types of drugs used were mainly tonifying deficiency(20.04%),diuresis and dampness(17.81%),activating blood circulation and removing blood stasis(13.88%),clearing heat(11.46%),etc;The medicinal properties are mainly cold and warm,the medicinal taste is mainly bitter and sweet,and the meridians are mainly attributed to the liver,spleen and stomach;A total of 27 association rules of core drugs for the treatment of NAFLD were found,and three core prescriptions were clustered.The efficacy was mainly to reduce fat and turbidity,promote water and dampness,soothe the liver and regulate qi,promote blood circulation and remove blood stasis,and clear away heat and dampness.The experimental study found that after modeling,the hair color of the rats was dim and loose,the feces were sticky and smelly,sleepy,obese,and the body weight increased significantly.The serum total cholesterol(TC),serum triglyceride(TG),alanine aminotransferase(ALT),and aspartate aminotransferase(AST)of the rats were significantly higher than those of the normal control group,and the P values of liver weight,TC,TG were < 0.01,and the P values of ALT were < 0.05,which proved to be statistically significant.The liver of rats in the model group was slightly swollen,tense,swollen,dark yellow and greasy.According to the results of opls-da,the screening conditions for lipidomics data were set as P < 0.01 and fold change > 2.A total of 108 potential biomarkers of phlegm dampness syndrome in NAFLD were analyzed through screening,including triglyceride(TG),diacylglycerol(DG),zymosterol(zyme),phosphatidylcholine(PC)Phosphatidylethanolamine(PE)and so on.Conclusion: the core syndrome types of NAFLD are phlegm dampness syndrome,blood stasis syndrome,liver stagnation and spleen deficiency syndrome,and damp heat syndrome,especially the phlegm dampness syndrome is the most common.The clinical drugs are mainly tonifying deficiency drugs,diuresis and dampness permeability drugs,activating blood circulation and removing blood stasis drugs,and heat clearing drugs.The main medicinal properties are bitter cold,sweet and warm;It is suggested that NAFLD is closely related to liver,spleen and stomach.According to the cluster analysis of prescriptions,the methods of clearing heat and activating blood circulation,soothing liver and regulating qi,promoting water and dampness,reducing turbidity and lipid are commonly used in the treatment of NAFLD in traditional Chinese medicine.Lipidomics experimental study found that the proportion of lipid triglycerides in the differential lipid markers between NAFLD phlegm dampness syndrome and the control group was the largest,and it was inferred that its saturation degree was probably related to the fat deposition in the liver.The increase in the overall level of phospholipids may be related to the abnormal lipid anabolism in the liver,which may suggest the progression of NAFLD.By calculating the Pearson correlation coefficient between lipids,it can be seen that there is a large degree of correlation between the different lipids.This study found that the liver lipid metabolism of NAFLD rats with phlegm dampness syndrome was significantly changed,and the 108 differential lipid metabolism markers screened may become a new basis for the diagnosis and treatment of NAFLD with phlegm dampness syndrome.