The Preparation Of Low-molecular-weight Fucoidans And Therapeutic Effect On Kidney Fibrosis

Renal fibrosis is a pathogenesis that chronic kidney disease(CKD)develops to end stage renal disease(ESRD).In the process of fibrosis,kidney cells in the cause of fibrosis factors or growth factors,the cell phenotype transformation,and ultimately lead to fibrosis.In addition,the production and degradation imbalance of extracellular matrix(ECM)components will further promote renal fibrosis.Acute renal injury(AKI),refers to the sudden decline in renal function in the short term.All over the global range,AKI morbidity continues to rise,the mortality rate is so high.As so far,there is no effective drugs for AKI prevention or treatment,for severe patients can only choose kidney replacement therapy or hemodialysis treatment methods.Our precious studies found that fucoidan(FPS)and low molecular weight fucoidan(LMWF)have a good therapeutic effect on chronic renal failure and diabetes mellitus,but the process and mechanism are still unclear.In this paper,low molecular weight fucoidan and its fractions were prepared and explored in the study of renal fibrosis.(1)Based on the extraction rate and the results of diastolic vasoactive screening,the preparation process of LWMF was optimized,and the optimized process was verified by preparing three batches.Two fractions F0.5 and F1.0 were prepared by fractional purification of LWMF with anion exchange column chromatography.(2)AKI model was induced by 50% glycerol hindlimb injection,and the typical AKI model was observed in rats.The fractions F0.5 and F1.0 was received through intraperitoneal injection.The F1.0 fraction can significantly reduce the BUN,SCr levels,kidney weight and body weight maintained at normal levels,blood glucose level is as same as normal group.The results indicated that F1.0 fraction can be effective in the treatment of AKI.(3)HK-2 cell transdifferentiation(EMT)were induced by TGF-β1 or FGF-2,the cells were observed significant fibrosis morphology.LMWF,F0.5 and F1.0 could significantly reduce the expression of fibronectin(Fn)and α-smooth muscle protein(α-SMA)in HK-2 cells at both protein and gene levels which are EMT markers,they showed significantly anti-renal fibrosis effect.The LMWF,F0.5 and F1.0 could indirectly regulate the expression of intracellular glycoprotein SDC-1 and decrease the expression of matrix metalloproteinase-9(MMP-9)by decreasing the expression of heparanase(HPSE)to reduce fibrosis symptoms.(4)Fucoidan(FPS)could inhibit the expression of PKC-α and PKC-β1 in NRK-52 E cells which induced by high glucose.The expression of TGF-β1 was also down-regulated in FPS-treated cells.FPS could also regulate P-selectin expression and promote its regulation for high glucose-induced DN.The results showed that FPS could regulate hyperglycemia-induced diabetic nephropathy by PKC-related signaling pathway and TGF-β signaling pathway.