Research On The Prevalence Of Non-alcoholic Fatty Liver Disease In Middle-aged And Elderly People And Study On The Effect And Mechanism Of Gynostemma Pentaphylla(Thunb.)makino In The Treatment Of Non-alcoholic Fatty Liver Disease

Objective1.To explore the prevalence and risk factors of non-alcoholic fatty liver(NAFLD)in middle-aged and elderly people and provide a basis for clinical prevention and control of NAFLD.2.To evaluate the effect of Gynostemma pentaphylla(Thunb.)Makino(GP)on NAFLD and explore the potential mechanism.Method1.Clinical research:A cross-sectional survey was conducted on the resident population over40 years old in Ningyang County to collect basic personal conditions,physical examination,blood biochemical indicators(such as fasting blood glucose,serum lipid profile,HBA1 c,etc.)and abdominal ultrasound and cervical artery ultrasound data.The prevalence and risk factors of NAFLD were analyzed by SPSS 22.0.2.Experimental research:A high-fat diet was fed for 12 weeks to induce a mouse model of NAFLD which were orally administered with GP decoction at a dose of 11.7 g/kg or an equivalent amount of distilled water once a day for another 16 weeks.The triglycerides,total cholesterol content in the liver and liverhistopathology,serum lipid profile and serum insulin level,fecal microbiome,hepatic microRNAs and relative target genes were analyzed.Result1.The prevalence of NAFLD in people over 40 in Ningyang County was 39.43%.Compared with non-NAFLD group,the age of NAFLD group was lower and the prevalence of NAFLD in women was higher than men(P<0.01).Waist circumference,BMI,fasting blood glucose,Hb A1 c,HOMR-IR,blood triglyceride levels,alanine aminotransferase,uric acid,serum creatinine levels were higher(P<0.01)in NAFLD group than those in non-NAFLD group,while high-density lipoprotein cholesterol levels were lower(P<0.01).Besides,the prevalence of diabetes,hyperuricemia(P<0.01)and hypertension(P<0.05)were also higher in NAFLD group.2.The prevalence of NAFLD increases gradually with age between 40 and 49 years old with the prevalence in male is higher than that in women.After 50 years old,the prevalence of NAFLD in male is gradually lower than women.Besides,with the BMI increasing,the prevalence of NAFLD also increased.3.Multivariate logistic regression analysis showed that age was a protective factor for NAFLD(P<0.01),while gender,waist circumference,glycosylated hemoglobin,HOMA-IR,triglyceride and uric acid were risk factors for NAFLD(P<0.05).For women,high-density lipoprotein cholesterol was a protective factor for NAFLD(P<0.05),while BMI,uric acid,HOMA-IR,and glycosylated hemoglobin were the major risk factors.4.Compared with the model group,GP improved the liver triglyceride content of NAFLD mice(P<0.05).H & E and oil red O staining showed that GP reduced lipid droplets and balloon-like damage in liver significantly which was consistanct with the result of NAFLD activity score(NAS)(P<0.05).In addition,glucose tolerance and insulin sensitivity were also improved by GP.5.Compared with the model group,GP treatment altered the composition of gut microbiota and the relative abundance of some of the key components thatare implicated in metabolic disorders,especially phylum Firmicutes(Eubacterium,Blautia,Clostridium and Lactobacillus).6.Several hepatic microRNAs were downregulated by GP treatment such as miR-130 a,miR-34 a,miR-29 a,miR-199 a,among which the expression miR-34 a was altered by more than four-fold compared to that of HFD group(3:14).The correlation analysis showed that miR-34 a was strongly related to the change of gut microbiota especially phylum Firmicutes(R=0.796).Additionally,the target genes of miR-34a(HNF4α,PPARα and PPARα)were restored by GP both in m RNA and protein levels.Conclusion1.The prevalence of NAFLD is high in middle-aged and elderly,and the risk factors are not ideally controlled.This study found that the mean values ??of waist circumference,BMI,fasting blood glucose and glycosylated hemoglobin in the NAFLD population and non-NAFLD population are at the upper limit of the threshold or even over normal,which means that these people are in the high exposure rate of NAFLD risk factors.Thus,the risk factors should be actively controlled to prevent NAFLD in time,especially for women over50 years old.2.Our study reveals a novel role of GP in alleviating hepatic steatosis and raised the possible mechanism of the beneficial effect of GP through modifying gut microbiota,which was associated with the suppression of hepatic miR-34 a.