关键词: 1H NMR, 纳米铜, 代谢组学, 模式识别

Abstract: BACKGROUND AND AIM: 1H nuclear magnetic resonance (1H NMR) spectroscopic methods were used to analyze serum obtained from rats treated with a range of doses of nano-copper particles in order to reveal the characteristics of the damage caused by nano-copper and identify the latent NMR biomarkers associated with the earlier damage. MATERIALS AND METHODS: 30 male Wistar rats were randomly assigned into five groups (6 rats per group), rats were given daily orogastric vehicle(1％ Hydroxypropylmethylcellulose), nano-copper (50, 100, 200 mg/kg) or micron-copper(200 mg/kg) for 5 days, and sacrificed on Day 6. The serum samples from all rats were collected and their 1H NMR spectra were acquired. PC analysis, blood biochemical analysis and histopathology examination for liver and kidney were performed simultaneously. RESULTS: For the rats dosed with 200 mg/kg nano-copper, increased levels in serum ALT, AST, TP, TG, TBA, TBILI, BUN and CREA, together with decreased ALP and TCHOL were marked compared with controls. Histopathology examination found hepatocellular dot necrosis, and widespread necrosis in the renal proximal tubules with protein cast in the tubule lumen, in which orange crystal deposition could also be found. For rats fed 50 and 100 mg/kg nano-copper, abnormalities included increased serum level of TCHOL and TG, as well as renal proximal tubular epithelial cellular swelling. The rats dosed with 200 mg/kg micron-copper particles showed slight damage. The metabonomic analysis of the serum samples revealed nano-copper disturbing cellular energy metabolism and serum lipid metabolism. These results were in agreement with the changes of serum biochemical and histopathology examinations. CONCLUSION: Liver and kidney were the potential target organs of nano-copper exposure. The damages of the target organs were associated with the disturbance of the cellular energy metabolism.

Key words: 1H NMR, metabonomic, pattern recognition, nano-copper