关键词: 人参皂苷, 静默信息调节剂 1, 叉头盒蛋白O1, 镉暴露, 肾损伤

Abstract: Objective To explore the protective effect of ginsenosides against renal injury induced by cadmium exposure via the Silent Information Regulator 1（Sirt1）-forkhead box protein O1（FoxO1） signaling pathway. Methods Totally 40 rats were randomly divided into control group,cadmium exposure group,low-dose ginsenoside group and high-dose ginsenoside group according to body weight. Except for the control group,the other groups were exposed to cadmium dichloride（25 mg/kg） by continuous gavage to establish renal injury model. During the cadmium dichloride exposure period,rats in low-dose and high-dose ginsenoside groups （1 000 and 2 000 mg/kg） were given corresponding doses of ginsenosides by gavage every day,and the control group and cadmium exposure group were given equal volumes of normal saline by gavage. After the experiment,the 24-hour urine protein,serum urea nitrogen（BUN）,serum creatinine（Scr）,renal superoxide dismutase（SOD）,glutathione peroxidase（GSH-Px）,tumor necrosis factor-α（TNF-α）,and renal cell apoptosis rate were measured. The renal cytochrome C（Cyt-c）,cysteinyl aspartate specific proteinase-9（caspase-9）,cysteinyl aspartate specific proteinase-3（caspase-3） levels were determined by enzyme-linked immunosorbent assay. The renal SIRT1,FOXO1,and nuclear factor kappa B（NF-κB） mRNA and protein levels were determined by RT-PCR and immunohistochemistry. Results The indexes of rats in the cadmium exposure group and the control group were as follows：24 h urine protein（14.74±2.54） vs （96.83±6.50）mg/24 h,serum BUN（9.49±2.04） vs （37.37±3.35） mmol/L,SCR level（6.39±0.67） vs （27.48±1.98）μmol/L,renal TNF-α level（12.59±2.11） vs （169.50±14.20）μg/L,renal cell apoptosis rate（3.24±0.53） vs （49.87±4.65）%,renal Cyt-c（56.87±5.66） vs （359.21±21.01）μmol/L,Caspase-9（18.30±3.22） vs （145.74±17.59）μmol/L,Caspase-3 protein （29.54±4.25） vs （214.06±30.02）mol/L,FOXO1 mRNA and protein level （0.99±0.13） vs （5.32±0.34）,（0.89±0.43） vs （ 6.26±0.85） points,NF-κB mRNA and protein level（1.05±0.12） vs （4.23±0.39）,（1.36±0.55） vs （5.74±0.47）points,which in the cadmium exposure group were higher than those in the control group. The renal SOD was （266.98±25.54） vs （63.87±19.40）μmol/L,GSH-Px was （489.59±48.37） vs （128.80±20.87）μmol/L,SIRT1 mRNA and protein level was （4.32±0.43） vs （0.95±0.11）,（5.77±0.53） vs（0.85±0.18）points,which in the cadmium exposure group were higher than those in the control group. All differences were statistically significant（all P<0.05）. The 24 h urine protein,serum BUN and SCR levels,renal TNF-α level,renal cell apoptosis rate,renal Cyt-c,Caspase-9,Caspase-3 protein,FOXO1 and NF-κB mRNA and protein levels of rats in the low- and high-dose ginsenoside groups were lower than those in the cadmium exposure group,while the renal SOD,GSH-Px and SIRT1 mRNA and protein levels were higher than those in the cadmium exposure group,and the difference was statistically significant（all P<0.05）. The 24-hour urine protein,serum BUN and SCR levels,renal TNF-α level,renal cell apoptosis rate,renal Cyt-c,Caspase-9,Caspase-3 protein,FOXO1,and NF-κB mRNA and protein levels in the high-dose ginsenoside group were lower than those in the low-dose ginsenoside group,and the renal SOD,GSH-Px,and SIRT1 mRNA and protein levels were higher than those in the low-dose ginsenoside group,and the differences were statistically significant（all P<0.05）. Conclusion The ginsenosides can inhibit oxidative stress,inflammation,and apoptosis,and have a significant protective effect on renal damage in rats exposed to cadmium,its mechanism is related to ginsenosides promoting SIRT1 expression and then inhibiting the activation of FOXO1-NF-κB pathway.

Key words: Ginsenosides, Silent information regulator 1, Forkhead box protein O1, Cadmium exposure, Renal injury