Objective To explore the therapeutic effect and mechanism of matrine on diabetes nephropathy in rats based on the signal pathway of high mobility group box-1(HMGB1)/Toll like receptor 4(TLR4).Methods The rats with diabetes nephropathy were fed with high fat and high sugar and injected with streptozocin(STZ)solution.The rats were grouped into control group,model group,matrine group(200 mg·kg-1),and HMGB1 inhibitor group(glycyrrhizic acid,10 mg·kg-1),after anesthesia,blood samples were collected to detect blood glucose and lipid levels,renal function indicators,and inflammatory cytokines levels,respectively.Hematoxylin eosin staining,periodic acid-Schiff staining,and Masson staining were applied to observe the pathological changes of renal tissue;the levels of Th1 and Th2 cells in rat spleen tissue were detected by flow cytometry;Western blot was applied to detect the expression of HMGB1/TLR4 pathway related proteins.Results The levels of fasting blood-glucose(FBG)in control group,model group,matrine group and glycyrrhizic acid group were(5.15±0.61),(26.24±2.15),(6.10±0.85)and(5.85±0.74)mmol·L-1,respectively;total cholesterol(TC)levels were(1.56±0.14),(4.15±0.36),(1.89±0.15)and(1.82±0.13)mmol·L-1,respectively;triacylglycerol(TG)levels were(1.46±0.14),(11.01±1.00),(3.04±0.21)and(3.15±0.18)mmol·L-1,respectively;serum creatinine(SCr)levels were(23.45±3.26),(69.78±7.32),(38.71±5.45)and(41.36±6.02)mmol·L-1,respectively;blood urea nitrogen(BUN)levels were(6.27±1.03),(17.02±1.72),(9.32±1.04)and(8.35±1.34)μmol·L-1,respectively;tumor necrosis factor α(TNF-α)levels were(102.35±14.68),(263.78±18.63),(134.02±11.47)and(122.35±15.04)pg·mL-1,respectively;Th1/Th2 cell ratios were 2.71±0.45,14.23±1.01,4.38±0.64 and 4.03±0.49,respectively;the relative expression levels of HMGB1 protein were 0.25±0.03,1.33±0.16,0.64±0.06,0.61±0.08,respectively;the relative expression levels of TLR4 protein were 0.33±0.06,1.25±0.18,0.51±0.07,0.47±0.09,respectively.Treatment group compared with the control group,the differences of the above indexes were statistically significant(all P<0.05);Matrine group and glycyrrhizic acid group were compared with model group,and the differences were statistically significant(all P<0.05).Conclusion Matrine can alleviate renal inflammation and pathological damage in diabetes nephropathy rats by regulating the balance of Th1/Th2 cells,which may be related to inhibiting the activation of HMGB1/TLR4 signaling pathway.
matrinehigh mobility group box-1/Toll like receptor 4 pathwaydiabetes nephropathyTh1/Th2 cells