Effects of acteoside on the expressions of high mobility group box 1 and nuclear factor-κB in the renal tissues of diabetic nephropathy mice / 中华肾脏病杂志

ABSTRACT

Objective:To investigate the effect of acteoside on the expressions of high mobility group box 1 (HMGB1) and nuclear factor-κB (NF-κB) in the renal tissue of diabetic nephropathy mice.Methods:Among 20 healthy 8-week old C57BL/6J mice, 5 mice were randomly selected as normal control group, the rest were established as type 1 diabetes mellitus (T1DM) models by a single intraperitoneal injection of streptozocin (STZ, 150 mg/kg). T1DM mice were randomly divided into three groups 5 mice without treatment, 5 mice treated with acteoside and 5 mice treated with irbesartan. After continuous administration for 8 weeks, serum, urine, and kidney tissue were collected for biochemical, pathological, and related mRNA and protein detection. The renal tubular epithelial cells (NRK-52E cells) were divided into control group (1 g/L glucose), high glucose group (4.5 g/L glucose) and high glucose+acteoside group (4.5 g/L glucose+32 μmol/L acteoside). Real-time PCR and Western blotting were used to assess the expressions of HMGB1 and NF-κB after 48 hours and 72 hours culturing.Results:Compared with normal control group, blood glucose, 24-hour quantitative urinary protein, blood urea nitrogen (BUN), serum creatinine (Scr) and blood and urine HMGB1 were significantly increased in model group (all P<0.05), along with interstitial inflammatory cell infiltration and messangial matrix expantion, and the expressions of HMGB1 and NF-κB were significantly enhanced (all P<0.05). Compared with model group, histopathologic changes were alleviated and the mRNA and protein expression levels of HMGB1 and NF-κB were lower in the acteoside group (all P<0.05), while the blood glucose level was maintained at high level ( P>0.05), excluding reduced quantitative 24-hour urinary protein, BUN, Scr, and serum and urine HMGB1 (all P<0.05). Compared with control group, the mRNA and protein expressions of HMGB1 and NF-κB were increased in high glucose group of NRK-52E cells (all P<0.05). Compared with high glucose group, the mRNA and protein expressions of HMGB1 and NF-κB in high glucose+acteoside group were down-regulated (all P<0.05). Conclusion:Acteoside may alleviate the nephropathy in STZ-induced diabetic nephropathy mice by down-regulating the expressions of HMGB1 and NF-κB.