The Therapeutic Effect Of Artesunate On Diabetic Nephropathy Rats And The Mechanism

Objective:To investigate the therapeutic effect and mechanism of artesunate(Art) on diabetic nephropathy(DN) rats. Mthods:Male SD rats were injected low dosage streptozotocin and fed with high fat and high sugar diets to establish diabetic nephropathy rats. After success established the DN animal model, then the experimental rats were randomly divided into six groups, normal control group (group A), diabetic nephropathy model group(group B),the rats in group C, D, E were intragastrically administrated with Art with the dose of 10mg/ (Kg.d),20mg/(Kg.d) and 30mg/(Kg.d) for consecutive 8 weeks, the rats in group F were intragastrically administrated with enalapril 10mg/ (Kg.d) for consecutive 8 weeks. The all rates were killed after 8 weeks.The plasma glucose was monitored routinely.24-hour urine protein quantitative, serum creatinine and blood urea nitrogen were measured to evaluate renal function, Fasting blood glucose、bodyweight、 kidney index were measured, Renal histopathology were perfomed by HE staining. Immunohistochemisty and euzymelinked immunosorbent assay(ELISA) were performed to examine the expression levels of monocyte chemoatracttant protein-1(MCP-1) and tumor necrosis factor (TNF-a)in renal tissue of rats;. respectively. Expression level::of Toll-like-receptor4(TLR4) in renal tissue of rats were examined by western blotting. Results:The fasting blood glucose、kidney index、 24-hours proteinuria, serum creatinine and urea nitrogen, MCP-1、TNF-α、 TLR4 in renal tissue of rats were increased in group B when compared with group A(P<0.01). There was no significant statistical difference of fasting blood glucose between each treatment groups (P> 0.05) Compared with the group B, the expression of 24-hours proteinuria, serum creatinine, urea nitrogen and serum glucose had decreased to some extent in each treatment groups(P<0.01). There was significantly statistical difference in group C when compared with group D、E(P<0.01).But It was not found statistical difference of serum creatinine, blood urea nitrogen between group E and group F(P>0.05). Artesunate could significantly decrease the expressions of MCP-1、TNF-α TLR4 in each treatment group. Showing statistical difference when Compared with group B(P<0.05).In group B, we could see some glomerular hypertrophy, mesangial area thickening, lots of deposits of inflammatory cells were detected in renal interstitial, all above changes were decreased in each treatment group. Conclusion:artesunate has benefical effects on diabetic nephropathy. artesunate reduces the expression of 24-hours proteinuria, serum creatinine, blood urea nitrogen, The mechanism of anti-inflammatory of artesunate may be related to the inhibition of inflammatory factor MCP-1 and TNF-α and inhibit the expression of TLR4 at the level of protein in renal tissue, further relive the pathological amage of kidney and delay the progress of diabetic nephropathy to some extent.