Effects of Ginkgo Biloba Extract on Renal Fibrosis in Mice with Unilateral Ureteral Obstruction by Regulating TGF-β1/HGF Signaling Pathway
Objective:To investigate the effects of ginkgo biloba extract(GBE)on renal fibrosis in mice with unilateral ureteral obstruction(UUO)by regulating transforming growth factor-β1(TGF-β1)/hepatocyte growth factor(HGF)signaling pathway.Methods:The UUO mouse model was constructed by unilateral ureteral ligation,the mice were randomly divided into model group,irbesartan group(20 mg/kg),GBE low,medium and high dose groups(25 mg/kg,50 mg/kg,100 mg/kg)after successful modeling,with 10 mice in each group.Another 10 mice were taken as sham operation group(only the left ureter was separated but not ligated).Renal function in-dexes:β-N-acetylglucosaminidase(NAG),creatinine(Scr),urea nitrogen(BUN)were detected;The levels of serum tumor necrosis fac-tor-α(TNF-α),interleukin(IL)-1β and IL-6 were detected by enzyme-linked immunosorbent assay(ELISA).The pathological changes of renal tissue were observed by hematoxylin-eosin(HE)staining.The fibrosis of renal tissue were observed by masson(Masson)staining.The expressions of α-smooth muscle actin(α-SMA)and TGF-β1 were detected by immunohistochemistry.The expression of type Ⅰ col-lagen(Col-Ⅰ),α-SMA,TGF-β1,cell signal transduction molecule 2(Smad2),phosphorylated Smad2(p-Smad2)and HGF protein in renal tissue were detected by Western blot.Results:Compared with sham operation group,the renal tubular lumen in model group was dilated or atrophied,inflammatory cell infiltration,collagen fiber deposition was obvious,NAG,Scr,BUN,TNF-α,IL-1β,IL-6,renal fibrosis level,Col-Ⅰ,α-SMA,TGF-β1,p-Smad2/Smad2 expression were significantly increased,and HGF protein expression was significantly decreased(P＜0.05).Compared with model group,the pathological damage of renal tissue in irbesartan group and GBE low,medium and high dose groups was reduced,the collagen deposition fibers were reduced,NAG,Scr,BUN,TNF-α,IL-1β,IL-6,renal fibrosis level,Col-Ⅰ,α-SMA,TGF-β1,p-Smad2/Smad2 expression were significantly decreased,and HGF protein expression was significantly in-creased(P＜0.05),among which irbesartan group and EG high dose group improved most significantly.Conclusion:GBE can reduce renal function damage,inhibit inflammatory response,and improve renal fibrosis in UUO mice,the mechanism may be relate to regulating the balance of TGF-β1/HGF signaling pathway.
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