关键词: 蛇床子素, 糖尿病肾病, 炎症, NF-κB, p38/MAPK

Abstract: AIM: To investigate the therapeutic effects of oral osthole on streptozotocin (STZ)-induced type 1 diabetes mellitus(T1DM) mice and explore its internal mechanism. METHODS: The diabetes model induced by STZ was established. Mice were randomly divided into control group, STZ model group, STZ+osthole group (20 mg/kg). Body weight, blood glucose, urine protein, blood urea nitrogen and creatinine were observed to detect renal function. The degree of renal tissue damage was detected by H&E staining and PAS staining, and the degree of renal fibrosis was detected by Sirius Red staining. CD68 and F4/80 immunofluorescence staining was used to observe the infiltration of macrophages in kidney tissue. The mRNA expressive levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) in renal tissue were detected by RT-qPCR. The protein expressive levels of phospho-NF-κB p65, NF-κB p65, IκBα, phospho-IκBα, phospho-p38 and p38 were detected by Western blot in renal tissue. RESULTS: Compared with the STZ model group, the levels of urinary protein, blood urea nitrogen, creatinine were significantly decreased after osthole treatment (P<0.05 or P<0.01). The renal structure disorder, mesangial matrix area, collagen fiber accumulation, and macrophage infiltration were significantly improved (P<0.05 or P<0.01). The expression of mRNA of pro-inflammatory cytokines TNF-α and IL-6 were significantly decreased (P<0.05 or P<0.001). The expression of phospho-NF-κB p65, phospho-IκBα and phospho-p38 were significantly down-regulated (P<0.05 or P<0.01), while the protein expression level of NF-κB p65, IκBα was up-regulated (P<0.05). CONCLUSION: Osthole has a protective effect on kidney injury caused by diabetes and inhibits NF-κB and p38/MAPK signaling pathway.

Key words: osthole, diabetic nephropathy, inflammation, NF-κB, p38/MAPK