Tripterygium Glycosides Improves Renal Injury In Rats With Idiopathic Membranous Nephropathy By Inhibiting TLR4/MyD88 Signaling Pathway

Objective:Rat models of idiopathic membranous nephropathy(IMN)were established by caudal intravenous injection of cationic bovine serum albumin(C-BSA),and tripterygium glycosides were given as intervention.To explain the impact on the TLR4/MyD88 signaling pathway and its therapeutic effect.Methods:Twenty healthy SD rats were randomly split into normal(n = 5)and modeling(n = 15)groups.The rat model of idiopathic membranous nephropathy was established by tail vein injection of C-BSA once every other day after the rats in the modeling group were preimmunized for one week.At the end of the modeling period,each rat was tested for 24-hour urine protein quantification(24h UTP),and one rat in the modeling group was randomly selected for renal pathology examination.After successful modeling,the modeling group’s rats were randomly divided into two groups: the model group(n=7)and the tripterygium glycosides treated group(n=7).The rats in the tripterygium glycosides treated group were given tripterygium glycosides tablets 50 mg/kg/d by gavage,and the rats in the normal group and the model group were given saline in the same volume by gavage for four weeks.After gavage,urine specimens were collected and 24-hour urine protein quantification was performed,and blood urea nitrogen(BUN),creatinine(Scr),total cholesterol(TC),and triglyceride(TG)levels in serum were measured,the changes in renal histopathological damage were observed under light microscopy,the expression level of TLR4 protein was detected by western blotting(WB),the expression of TLR4 and MyD88 protein in renal tissues was detected by immunohistochemistry(IHC),and the expression of IL-6 was detected by enzyme-linked immunosorbent assay(ELISA).Results:1.Rats given tripterygium glycosides treatment had considerably lower 24 hour UTP levels than those in the model group;these changes were statistically significant(P<0.05).In the meantime,the BUN and Scr in the rats in the tripterygium glycosides treated group were decreased to varying degrees in comparison to the model group,but the differences were not statistically significant(P>0.05).2.Under the light microscope,the glomeruli of the normal group were structurally intact,the cystic cavity was normal in shape and size,and the basement membrane was not thickened.The glomeruli of the rats in the model group were disorganized,enlarged,with more cells in the glomeruli,narrowing of the capsule cavity,and varying degrees of basement membrane thickening.Compared with the model group,the glomerular basement membrane thickening in the rats treated with tripterygium glycosides tablets were significantly improved and the pathological changes were significantly reduced compared with the model group.3.TLR4 and MyD88 protein expression was higher in the kidney tissue of IMN rats than in the blank control group,which was statistically significant(P<0.05).The relative expressions of TLR4 and MyD88 protein in the kidney tissues of rats treated with tripterygium glycosides were significantly lower in comparison to the model group(P<0.05).Conclusion:1.Tripterygium glycosides tablets can significantly reduce urinary protein and improve renal function in rats with IMN.2.Tripterygium glycosides tablets improved the thickening of the basement membrane in the kidney of IMN rats and attenuated renal pathological injury.3.Tripterygium glycosides tablets can reduce IL-6 and down-regulate TLR4 and MyD88 expression in renal tissues of IMN rats,and its therapeutic effect on membranous nephropathy may be related to the inhibition of the TLR4 / MyD88 pathway.