Hesperidin Improves The Inflammation And Fibrosis Mechanism Of Kidney Injury In Spontaneous Diabetic Mice

Diabetic kidney damage(DKD)is a common pathological damage of diabetes.glomerular mesangial cells are over-proliferated at early stage of DKD,this pathological changes cause extensive deposition of mesangial extracellular matrix proteins,and then leading to glomerular basement membrane thickening.Meanwhile,the kidney filtration rate decreased,and this leading to microalbuminuria,and even develop into macroalbuminuria.Mesangial extracellular matrix protein accumulation(ECM)is the basis of diabetic nephropathy,it plays an important role in diabetic nephropathy.Hyperglycemia-induced kidney damage is associated with inflammation and renal fibrosis.Previous studies have confirmed that hesperidin has anti-inflammatory,inhibit the role of cell proliferation and antioxidant effects.ln this paper,based on the current situation of domestic and foreign research,through in vivo experiments,we explored the efficacy and mechanism of hesperidin on anti-inflammatory glomerular mesangial proliferation prevention,delay the process of fibrosis,reduce urinary microalbumin excretion and prevention and treatment of diabetic nephropathy.Method:1 Pathological model of diabetic nephropathy in db/db diabetic miceWe selected db/db diabetic mice as diabetic nephropathy model animals,the levels of GLU.TC.TG.LDL-C.CRE and BUN were measured and compared with db/m blank control mice.Anatomy laboratory mice,the degree of nephropathy in model mice was analyzed and renal glomerular morphology and glomerular mesangial hyperplasia was observed.Through the above experiments,we analyze the feasibility of db/db diabetic mice as a model of early diabetic nephropathy.2 Study on the effect of hesperidin on improving kidney injury in db/db diabetic mice by anti-inflammatory and anti-fibrosis24 weeks old male db/db mice were continuous given hesperidin(200mg/kg)for 14 weeks,The plasma levels of blood GLU.TC.LDL-C.MAIb.Ucr were measured.The renal H&E staining was performed to detect the morphology of the kidneys,and PAS staining was used to detect glomerular basement membrane thickening and mesangial cell proliferation.The expression of FN,type ? collagen(COL-?)and growth factor(TGF-?1)gene was detected by RT-PCR;Immunohistochemistry was used to detect the expression of fibronectin(FN)in renal cortex.The expression of F4/80,tumor necrosis factor(TNF-a)and interleukin-6(IL-6)gene was also detected by RT-PCR.Immunofluorescence was used to detect the expression of Kidney macrophage marker antigen(F4/80)in kidney.Through the above experimental method,we detected the efficacy of hesperidin in inhibiting renal mesangial cell proliferation,inhibiting renal basement membrane thickening and reducing urinary microalbumin.Finally explore the efficacy of hesperidin in improving renal pathological changes.Result:1 db/db diabetic mice showed characteristics of glomerular mesangial cell proliferation in renal injuryExperimental results of renal pathological examination showed that db/db diabetic mice showed early renal injury pathological features as significantly hypertrophied,glomerular basement membrane thickened and collagen deposition.Meanwhile,blood biochemical indexes of db/db diabetic mice showed that serum creatinine and urea nitrogen were not significantly increased,indicating that db/db diabetic mice did not show typical diabetic nephropathy characteristics.2 Hesperidin significantly improved diabetic nephropathy in db/db mice2.1 Kidney H&E staining showed:Hesperidin significantly improved the integrity of the glomerular capillary network structure in db/db diabetic mice.Renal PAS staining showed that hesperidin could significantly inhibit the glomerular basement membrane thickening and mesangial proliferation in db/db diabetic mice.On the one hand,the PCR results showed that hesperidin could down-regulate the expression of TGF-3 1,COL-? and FN in the kidney of db/db diabetic mice,and the results of renal immunohistochemistry showed that hesperidin could significantly decrease the expression of FN in glomeruli.All these results indicating that hesperidin delay the progress of glomerulosclerosis in db/db diabetic mouse by down-regulating the expression of fibrosis-related genes and reducing the expression of FN.On the other hand,PCR results showed that hesperidin could down-regulate the expression of F4/80,TNF-a and IL-6 genes in kidney of db/db diabetic mice,immunofluorescence results showed that hesperidin could significantly decrease the expression of F4/80 in glomeruli and inhibit the infiltration of macrophages to the kidneys,we also found that hesperidin can inhibits Inflammatory response induced mesangial extracellular matrix accumulation and its further damage to the kidneys.And eventually delay the process of renal injury.2.2 Hesperidin reduces urinary albumin excretion and improves renal filtration function in db/db diabetic mice.But,we also found that hesperidin had no significant effect on plasma glucose,total cholesterol and low density lipoprotein cholesterol in db/db diabetic mice.Conclusion:Hesperidin has the effects of reducing the excretion of urinary microalbumin and improving the function of renal filtration in db/db diabetic mice.We also found that hesperidin showed effects of inhibiting the accumulation of glomerular basement membrane,reducing the accumulation of ECM,delaying the process of glomerular fibrosis in db/db diabetic mice.Its mechanism may related to the following two aspects:one is the anti-inflammatory effects of hesperidin,as it reduce the infiltration of macrophage,achieving the effect of reducing mesangial matrix accumulation;another is its effects of inhibiting proliferation and anti-fibrosis.