A study on effects of liensinine on streptozotocin-induced diabetic nephropathy rats
Objective:To study the effect of liensinine on streptozotocin-induced diabetic nephropathy model rats.Methods:The rats in the model group were injected with streptozotocin via tail vein to establish the model,while the control group was given an equal volume of citrate buffer solution.After successful modeling,the diabetic rats were randomly divided into the model group(equal volume of saline),the captopril group(captopril 10 mg/kg),the low-dose liensinine group(liensinine 2 mg/kg),the medium-dose liensinine group(liensinine 4 mg/kg),and the high-dose liensinine group(liensinine 8 mg/kg),with 10 rats in each group.Another 10 healthy rats were selected as the blank group.Streptozotocin-induced diabetic nephropathy rats were treated with liensinine for 12 consecutive weeks.Changes in 24-hour urinary microalbumin,urinary protein content,and renal pathology were determined.The mRNA expression levels of nephrin,podocin and HPSE in the rats'renal cortex were detected by RT-PCR.The expressions of TGF-β1 and collagen type Ⅳ were determined by WB.This study aimed to investigate the mechanism of action of liensinine.Results:The urinary albumin and microalbumin excretion in rats were significantly reduced after liensinine treatment,which was significantly different from that in the model group and showed certain concentration-dependent characteristics.After treatment,glomerular basement membrane thickness,glomerular maximum diameter and collagen accumulation in rats in the liensinine groups were significantly reduced compared with the model group.The results of transmission electron microscopy showed that the foot process structure in the blank group was normal,and there was no apoptosis or shedding of podocytes in the model group.Compared with the model group,the width of the foot process was significantly reduced in the liensinine groups(P<0.01),and the number of podocytes was increased.The qPCR results showed that compared with the model group,the relative expressions of nephrin and podocin were increased and the relative expression of HPSE was decreased in the rat kidney tissues,the changes were most obvious in the high-dose liensinine group,and the differences were statistically significant(P<0.01).Conclusion:Liensinine may effectively reduce urinary protein and renal damage in diabetic nephropathy rats by up-regulating the expression of nephrin and podocin,down-regulating the level of HPSE,and restoring the glomerular filtration barrier,as well as attenuating renal fibrosis through down-regulating the expressions of TGF-β1 and collagen type Ⅳ.