The Effects Of Pterocarya Hupehensis Skan Decoction On Chronic Graft-versus-host Disease Lupus-like Mice

Objective:To investigate the effect of Pterocarya Hupehensis Skan(PHS)decoction on renal impairment in chronic graft-versus-host disease(cGVHD)lupus nephritis mice and to explore its possible mechanism.Methods: Twenty 8-week-old BCF1 female mice(hereinafter referred to as "F1 mice")were used as recipients,and BALB/c(female)mice were used as donors.The donor mouse spleen lymphocyte suspension was injected through the tail vein to establish cGVHD.The cGVHD lupus-like nephritis mice with successful modeling were randomly divided into the model PHS treatment group(MPG)and the model control group(MCG).Twenty-four healthy F1 female mice were randomly divided into normal control group(NCG)and normal PHS group(NPG),respectively.The MPG and the NPG mice were given PHS decoction for 2 weeks and 4 weeks respectively.The body weight of the mice was measured weekly.After the end of the feeding,the kidney tissues of the mice was taken for HE staining for pathological analyses.The expression of Smad7,Smad3 and TGF-β1 protein in the kidney was analyzed by Western blotting.ELISA method to detect the level of IL-1β and TNF-α,as well as Cr,BUN,ALT and AST in mice serum were detected by ELISA.Results: In the 8th week after model establishment,the proteinuria of cGVHD model mice was positive,and the serum anti-dsDNA antibody was significantly higher than that of normal mice,and the statistical difference was significant(P<0.01).Renal pathologic analysis in cGVHD model showed the increased glomerular volume,infiltrated massive inflammatory cells,edema-like degeneration of renal tubular epithelial cells,proliferation of endothelial cells and mesangial fibrous tissue,suggesting successful modeling and then starting PHS intervention.After 2 and 4weeks of administration with or without PHS,renal tissue HE staining in MPG mice showed that the kidney lesions were significantly relieved,and the interstitial inflammatory cell infiltration was significantly improved.Renal lesions in MCG mice were observed aggravated,obvious glomerular enlargement,renal cystic fissures,thickened basement membrane from mesangial ECM hyperplasia,glomerular andrenal vesicle adhesions.Increased expression level of TGF-β1 and Smad3 was found in the kidney tissue of the MCG mice,oppositely low expression of Smad7 was detected in NCG mice(P<0.05);TGF-β1 and Smad3 in the kidney tissue of the MPG mice decreased,and Smad7 increased,compared with the model control group(P<0.05).The serum levels of IL-1β and TNF-α in the MCG mice were significantly higher than those in the NCG and the NPG mice(P<0.01).Compared with the MCG mice,serum IL-1β and TNF-α levels in the MPG mice were significantly lower at 2and 4 weeks(P<0.01),and the level of which in 4-week feeding MPG mice was significantly lower than that in 2-week-feeding mice.Improvement of renal function was found in MPG mice with an decrease of BUN and Cr.Compared with the MCG mice,ALT and AST decreased in the PHS treatment group.No obvious drug-induced liver and kidney damage was found.Conclusion: PHS significantly improve the pathological structure of kidney tissue in cGVHD lupus nephritis mice,and reduced the degree of renal fibrosis and kidney inflammation in lupus mice.The mechanism may be achieved by inhibiting the activation of TGF-β1,Smad3 in kidney tissue,up-regulating the expression of Smad7,and reducing the production of IL-1β and TNF-α.