Effect of artesunate on expressions of Toll-like receptor 4 and interleukin-8 in renal tissues of diabetic nephropathy rats / 天津医药

ABSTRACT

Objective To investigate effect of artesunate on expressions of Toll-like receotor-4 (TLR4) and interleu?kin-8 (IL-8) in renal tissue of diabetic nephropathy rats. Methods Male SD rats of over 200 g in body weight (n=45) were injected with low dosage streptozotocin and fed with high fat and sucrose diets to establish diabetes nephropathy (DN) model. Among all rats of successful model, thirty-two were randomly selected and divided into four groups (n=8 in each group), Mod?el group (Group B), Artesunate at high dose treatment group [30 mg/(kg · d)] (Group C), Artesunate at low dose treatment group [10 mg/(kg·d)] (Group D), Enalapril treatment group [10 mg/(kg·d)] (Group E). Another eight rats without STZ injec?tion whose body weight is under 200 g were assigned as Normal group (Group A). Then, rats in Group A and B were given the same volume of normal saline [10 mg/(kg·d)] while rats in Group C, D and E were given 30 mg/(kg·d) Artesunate, 10 mg/(kg·d) Artesunate and 10 mg/(kg · d) Enalapril respectively intragastrically for consecutive 12 weeks. Fasting blood glucose, body weight, kidney index, 24-hours proteinuria, serum creatinine (Cr) and blood urea nitrogen (BUN) were measured. Expression level of TLR4 in renal tissue of rats were examined by Western blot;ELISA was used to quantify the concentration of IL-8 in serum and renal tissue of rats. Results Compared with rats in Group A, the levels of Fasting blood glucose, kidney index , 24-hours proteinuria, Cr and BUN as well as the level of TLR4 in kidney, levels of IL-8 in serum and kidney all significant?ly increased in rats in Group B, C, D and E(P<0.05). On the other hand, body weight were decreased in rats of Group B, C, D and E compared to rats in Group A(P<0.05). The level of TLR4 in kidney, levels of IL-8 in serum and kidney, 24-hours proteinuria, Cr and BUN in rats of Group C, D and E were significantly lower than those in rats of Group B(P<0.05). Furthermore, compared with rats in Group D, the levels of TLR4 in kidney, IL-8 in serum and kidney, 24-hours proteinuria, Cr and BUN were decreased in rats in Group C and E(P<0.05). Pearson correlation analysis showed that the expression lev?el of TLR4 positively correlated with IL-8 level in serum (r=0.969, P<0.05), IL-8 level in kidney (r=0.972, P<0.05), 24-hours proteinuria(r=0.965, P<0.05), Cr(r=0.944, P<0.05)and BUN(r=0.903, P<0.05). IL-8 level in kidney positively correlated with 24-hours proteinuria(r=0.962, P<0.05), Cr(r=0.929, P<0.05)and BUN(r=0.940, P<0.05). Conclu?sion Artesunate decreases expression of TLR4 and IL-8, reduce 24-hours proteinuria, inhibits the inflammation of the DN,relives the pathological lesions of nephron rats with diabetic nephropathy.