关键词: 青蒿素, 糖尿病肾病, Toll 样受体4, 白细胞介素8, 炎症反应, 青蒿琥酯

Abstract: 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.

Key words: ARTEMISININ, diabetic nephropathies, Toll-like receptor 4, interleukin-8, inflammatory reaction, ARTE? SUNATE