Abstract:Objective To construct and evaluate a mouse model of renal fibrosis syndrome combined with Qi-deficiency and dampness-stasis, and explain the changes of protein and metabolic pathways by multi-omics.Methods 24 C57BL/6j mice were randomly divided into normal group (N), model group (M) and renal fibrosis disease and syndrome combined group (BZ) with 8 mice in each group. The experiment period was 6 weeks. A mouse model of renal fibrosis with Qi deficiency and dampness stasis was established by "CsA + high-fat diet + swimming exhaustion + constant temperature and humidity" . The model was evaluated by measuring the general signs, observing renal function, tongue RGB (red, green, blue) values, hemorheology indexes, blood lipids, inflammation and oxidation indexes.And combined with renal tissue HE, Masson, PAS, oil red O staining, TUNEL apoptosis, and TGF- β immunofluorescence. Renal proteomics combined with serum metabolomics screened out differential proteins and metabolites and performed pathway enrichment analysis. Results The weight of BZ group began to decline at the 3rd week (P < 0.05), and significantly decreased at the 4th week (P < 0.01). At the same time, the amount of eating and drinking water decreased, the hair disordered and gloss decreased, the spirit decreased, the activity decreased, and the stool was thin. Scr, BUN, UACR and NAG in BZ group were higher than N group (P < 0.05 or P < 0.01), the Scr and NAG level was statistically significant compared with M group. The R value of tongue image in BZ group was significantly lower than N group (P < 0.01), and the B value was higher than N group (P < 0.05). The viscosity of whole blood multi-shear rate and HCT in BZ group were higher than those in N and M groups, and PV was higher than those in N group (P < 0.05 or P < 0.01). The levels of TC, LDL-C, CRP, IL-6 and MDA in BZ group were significantly increased compared with N and M groups (P < 0.01), and the activity of SOD was decreased compared with N group (P < 0.05). In BZ group, renal tubule vacuolation, inflammatory cell infiltration, glomerular basement membrane thickening, collagen fiber hyperplasia and lipid accumulation were evident. Renal cell apoptosis and TGF-β deposition were increased in BZ group. There were 299 different proteins in BZ and N groups, 180 of which were up-regulated and 119 down-regulated. There were 323 differential metabolites, of which 205 were up-regulated and 118 down-regulated. Primary bile acid biosynthesis,Taurine and hypotaurine metabolism,Biosynthesis of unsaturated fatty acids are co-enriched by differential proteins and differential metabolites, involving 3 differential proteins and 9 differential metabolites. Among them, Docosapentaenoic acid (22n-3),Eicosapentaenoic acid,Taurine,3-Sulfinoalanine,Taurocholic acid,Acnat1,Hsd17b12,Acnat2 showed high prediction accuracy.Conclusion It is feasible to construct RF animal model of Qi-deficiency and dampness-stasis by "CsA+high-fat diet + exhaustion of swimming + constant temperature and humidity" method. The Biosynthesis of unsaturated fatty acids andTaurine and hypotaurine metabolism may play an important role in RF animal model of Qi-deficiency and dampness-stasis.