Study Of The Renal Protective Effects Of Icarrin On Experimental Diabetic Rats And Its Mechanism

Objective: To investigate the effect of Icarrin on expression oftransforming growth factor-β1, matrix metalloproteinases and type IVcollagen of renal tissue in STZ-induced diabetic nephropathy rats.Methods: Diabetic rats, male, SD, were induced by intravenousinjection of streptozotocin (STZ,40mg/kg). Seventy-two hours after STZadministration all animals with plasma glucose level≥16.7mmol/l wereconsidered diabetic and included into the study. Then the rats were dividedrandomly into three groups: control, diabetes, diabetes+Icarrin (80mg/kg/d,i.g.). The rats were observed12weeks for developing diabetic nephropathy,the agents were administered8weeks from5th to12th week. Serum wascollected before rats sacrificed and BUN, Cr was examined. Both kidneyswere weighted to calculate the kidney hypertrophy index. The renal tissueswere collected to measure the activities of SOD, MDA and Hyp.Hematoxylin and eosin (HE) staining and Masson trichrome (Masson)staining were used to detect the renal pathological changes by lightmicroscope. TGF-β1, collagen IV, MMP-2and MMP-9were detected withimmunohistochemistry analysis. The levels of MMP-2and MMP-9mRNAwere detected by reverse transcriptasepolymerase chain reaction (RT-PCR).Results:1. Twelve weeks later, the level of blood glucose, KW/BW ofdiabetic group was significantly higher than that of control group (P<0.01);the level of KW/BW of Icarrin was significantly lower than that of diabet icgroup(P<0.01), there was no significance between the level of blood 2. BUN, Cr: The activities of BUN, Cr of diabetic group wassignificantly higher than that of control group (P<0.01); the activities ofBUN, Cr of Icarrin group was significantly lower than that of diabeticgroup (P<0.05).3. SOD, MDA, Hyp: The activity of SOD of diabetic group wassignificantly lower than that of control group (P<0.01); the activities ofMDA, Hyp of diabetic group was significantly higher than that of controlgroup (P<0.01). The activity of SOD of Icarrin group was significantlyhigher than that of diabetic group (P<0.01); the activities of MDA, Hyp ofIcarrin group was significantly lower than that of diabetic group (P<0.05).4. Light Microscopic Observation in the kidney: glomerularhypertrophy and fibrosis of renal tubule interstitium were easily observedin diabetic group; Icarrin improved these changes.5. Expression of TGF-β1, collagen IV, MMP-2and MMP-9:Expression of TGF-β1and collagen IV of diabetic group was significantlyhigher than that of control group (P<0.01); expression of MMP-2andMMP-9of diabetic group was significantly lower than that of control group(P<0.01). Expression of TGF-β1and collagen IV of Icarrin group wassignificantly lower than that of diabetic group (P<0.01); expression ofMMP-2and MMP-9of Icarrin group was significantly higher than that ofdiabetic group (P<0.01)Conclusion: Icarrin may have a protective effect on renal function ofDM rats. The mechanism may be related to that Icarrin can regulate theexpressions of TGF-β1, MMP-2, MMP-9, collagen IV.