Study On The Ancient Syndrome And Treatment Rules Of Baihu Jia Renshen Decoction And Its Effect On Adipose Tissue Inflammation In Obese Diabetic Mic

Objective : Through the literature research method,collect and sort out the prescriptions of Baihu Jia Renshen Decoction in ancient literature,and comprehensively analyze and summarize the main indications and compatibility rules of traditional Chinese medicine based on the cloud platform of ancient medical records,and study the compatibility rules of Baihu Jia Renshen Decoction,so as to provide new methods and ideas for clinical treatment of diabetes.To investigate the effect of Baihu Jia Renshen Decoction on toll like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor kappa-B(NF-κB)signaling pathway in adipose tissue of high-fat diet-induced loss of skeletal muscle-specific insulin-like growth factor-1 receptor function(MKR)obese diabetic mice.To provide a new scientific basis for understanding the potential mechanism of anti-diabetic effect of Baihu Jia Renshen Decoction.Methods : In the part of literature research,the database of Baihu Jia Renshen Decoction was established,including the source of the prescriptions,the composition of traditional Chinese medicine and the main indications.Based on the ancient medical case cloud platform,frequency analysis,cluster analysis,association rule analysis and complex network core prescription analysis were carried out.In the experimental research part,30 8-week-old male MKR mice were induced by high-fat diet for 12 weeks.After successful replication of obesity and type 2 diabetes mouse model,they were randomly divided into model group,Baihu Jia Renshen Decoction group and metformin group.Another 10 male FVB mice of the same age were used as normal control group.Each group of mice was given corresponding drugs or distilled water for 6 weeks.After fasting for12 h,fasting blood glucose(FBG)and oral glucose tolerance test(OGTT)were performed,and then anesthesia was performed.Liver function and blood lipid levels were detected by routine biochemical method.The morphological structure and pathological changes of epididymal white adipose tissue(WAT)were observed by hematoxylin-eosin staining.The levels of serum interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent assay.The expression of IL-1β,IL-6 and TNF-α in epididymal white adipose tissue was observed by immunofluorescence staining.Western blot was used to detect the relative expression of TLR4,MyD88,NF-κB,NF-κB p56,IL-1β,IL-6 and TNF-α protein in epididymal white adipose tissue.Results : Literature research results : A total of 80 Baihu Jia Renshen Decoction and its categorized formula were collected,8 in the Tang Dynasty,31 in the Song,Jin and Yuan Dynasties,and 41 in the Ming and Qing Dynasties.The most frequent disease treated by Baihu Jia Renshen Decoction and its categorized formula is diabetes,including upper diabetes,middle diabetes and lower diabetes,with a total of 14 prescriptions.Tonic drugs and heat-clearing drugs were the most frequently used drugs in the three periods of Baihu Jia Renshen Decoction and its categorized formula.The three periods were roughly equal,mainly attributed to the lung,stomach,spleen,heart and kidney;the core prescription of the class prescription developed from gypsum-anemarrhena-ginseng in the Tang Dynasty to gypsum-anemarrhena-ginseng-glycyrrhiza-puerarin-scutellaria baicalensis in the Song,Jin and Yuan Dynasties,and to gypsum-anemarrhena-ginseng-glycyrrhiza-japonica-japonica in the Ming and Qing Dynasties,which further reflected the therapeutic principles of clearing heat and nourishing yin.Experimental results : The results of glucose and lipid metabolism related indicators showed that compared with the normal control group,the FBG level,the area under the OGTT curve and the contents of total cholesterol(TC),triglycerides(TG)and low density lipoprotein cholesterol(LDL-C)in the model group were significantly increased(P<0.01).The content of high density lipoprotein cholesterol(HDL-C)was significantly decreased(P<0.01),while Baihu Jia Renshen Decoction could significantly improve the above indexes of obese MKR diabetic mice(P<0.01).The results of liver function related indicators showed that compared with the normal control group,the alanine aminotransferase(ALT)and aspartate transaminase(AST)in the model group were significantly increased(P<0.01);compared with the model group,the levels of serum ALT and AST in the Baihu Jia Renshen Decoction group were significantly decreased(P<0.01).The results of epididymal WAT inflammation-related indicators showed that compared with the normal control group,the model group had fat cell shrinkage and collapse,inflammatory cell infiltration,serum levels of IL-1β,IL-6,and TNF-α,and protein expression in epididymal WAT were significantly increased(P<0.01);compared with the model group,there was no obvious abnormality in the structure of adipocytes in the Baihu Jia Renshen Decoction group,and the infiltration of inflammatory cells was reduced.The serum levels of IL-1β,IL-6 and TNF-α and the protein expression in epididymis WAT were significantly down-regulated(P<0.01),and the effect was comparable to that of metformin group(P>0.05).The results of TLR4/MyD88/NF-κB signaling pathway related indicators showed that compared with the normal control group,the expression of TLR4,MyD88,NF-κB and NF-κB p56 protein in the model group was significantly increased(P<0.01);compared with the model group,the differences of TLR4(P<0.05),MyD88(P<0.01),NF-κB(P<0.01)and NF-κB p56(P<0.01)in the Baihu Jia Renshen Decoction group were statistically significant.Conclusion : Literature research shows that diabetes is a common disease treated by Baihu Jia Renshen Decoction.Physicians in the past dynasties added and subtracted according to the principle of three elimination points,and tonifying deficiency and clearing heat are the main compatibility rules of Baihu Jia Renshen Decoction.Experimental studies have shown that Baihu Jia Renshen Decoction can significantly reduce the fasting blood glucose level and improve insulin resistance in MKR diabetic mice,which is related to its ability to reduce the inflammatory state of white adipose tissue and down-regulate the expression of TLR4 / MyD88 / NF-κB signaling pathway proteins.