Abstract：Objective To investigate the protective effect of costunolide on kidneys in diabetic rats.Methods Twelve male SD rats (chosen from 70 rats) in the control group were fed with normal diet. The other 58 rats were injected with STZ via tail vein after fed with high-sugar and high-fat diet for 8 weeks. Then, these rats were randomly divided into diabetic model group, insulin group, costunolide low dosage group (10 mg) and costunolide high dosage group (20 mg). The general situation, body weight and blood glucose of rats were measured every week after administration. Drug intervention treatment was performed for 8 weeks. Then serum was collected to measure renal function, superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) content. Kidneys were embedded for pathological section with hematoxylin and eosin staining; renal inflammatory cytokines IL-6 and TNF-α expression were detected by ELISA; western blot was used to detect the protein content of Nrf2 and its downstream signaling molecules of HO-1, NF-кB p65signaling pathway related molecules in renal tissue.Results Blood glucose and renal function were significantly better than those in the diabetic group after costunolide treatment. Morphologic observation showed that rat kidney lesion was significantly improved in costunolide treatment group. Serum antioxidant index in costunolide treatment group significantly improved compared with the diabetic group (P<0.05), IL-6 and TNF-α expression were lower than thatof diabetic group (P<0.05). Protein expression of Nrf2, HO-1 increased and NF-кB p65, IKKβ decreased in Costunolide treatment group than that of diabetic group by Western blot(P<0.05). Compared with different CS dose groups, GSH level was higher than CS low dose group and IL-6 was significantly lower than CS low dose group (P<0.01), while the other indicators were not statistically significant.Conclusions Costunolide can significantly protect kidney lesion in diabetic rats, which may be done through upregulating Nrf2 enhanced antioxidant capacity and suppressing the NF-кB inflammatory pathways.
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