EFFECT OF BLOOD GLUCOSE FLUCTUATION ON APOPTOSIS OF RAT HEPATOCYTES IN VIVO

摘要

Background. Blood glucose levels in the human body continuously fluctuate within a certain range. Intermittent hyperglycemia has adverse effects on vascular endothelial cells and pancreatic beta cells. A few studies have found that blood glucose fluctuation induced apoptosis of both endothelial cells and pancreatic beta cells, possibly due to oxidative stress. This study aimed to determine the effects of blood glucose fluctuation on hepatocytes in vivo.Materials and Methods. To induce intermittent hyperglycemia, rats were intermittently treated with 50% glucose injection to fluctuate blood glucose between 5.5 mmol/L and 20.0 mmol/L. The rats with intermittent hyperglycemia were treated with either low dose (0.35 mg/kg'min) or high dose (0.70 mg/kg'min) N-acetylcysteine (NAC). The rats infused with saline were used as control. Apoptosis was assessed by TUNEL assay. Malondialdehyde (MDA) and superoxide dismutase (SOD) in the liver, as well as plasma ALT, AST, TBIL, and IBIL, were examined using colorimetric kits.Results. Liver function was lower in the rats with intermittent hyperglycemia than in control rats. Hepatocytes exposed to blood glucose fluctuation were more likely to undergo apoptosis compared to control group (0.07+-0.016 vs. 0.015+0.009, P<0.01). The expression of Caspase-3 and cleaved Caspase-3 was significantly higher in the IHG group than in the SAL group (0.11J +-0.015 vs. 0.07+-0.011; 0.064+-0.012 vs. 0.004+-0.001, P<0.05).The expression of Bax and the ratio of Bax to Bcl-2 were significantly higher in the IHG group than in the SAL group (0.20+-0.05 vs. 0.10+0.02; 0.55+-0.20 v.s. 0.20+0.05, both P<0.01). When treated with NAC, the liver function of rats with intermittent hyperglycemia improved remarkably, and hepatocyte apoptosis decreased.Conclusion. Blood glucose fluctuation appeal's to be detrimental to liver function, but this effect can be ameliorated by NAC.