氧化石墨烯对红细胞功能的影响

Effect of graphene oxide on the function of erythrocytes

摘要:

纳米材料的生物相容性是人们关注的热点。氧化石墨烯是一种被广泛应用于生物医学的纳米材料，但其毒性不容忽视。本文从溶血率、红细胞脆性、乙酰胆碱酯酶活性三方面研究了氧化石墨烯对血液系统的毒性。结果表明，红细胞的溶血率在氧化石墨烯浓度低于100 μg/mL时均低于8% (P<0.01)；低浓度氧化石墨烯 (<5 μg/mL) 对红细胞的脆性没有显著影响，高浓度氧化石墨烯 (如10 μg/mL) 会提高红细胞的脆性 (P=0.01)；氧化石墨烯能增加红细胞上乙酰胆碱酯酶的活性，浓度为20 μg/mL的直径>5 μm的氧化石墨烯 (LGO) 可将乙酰胆碱酯酶的活性提高42.67% (P<0.05)。之后利用分子动力学模拟研究氧化石墨烯与乙酰胆碱酯酶相互作用并提高其活性的机理，推测氧化石墨烯会附着在细胞膜上并提供一个电负性环境，帮助水解产物更快地从活性位点脱离，从而提高乙酰胆碱酯酶的活性。

Abstract:

The biocompatibility of nanomaterials has attracted much attention. Graphene oxide (GO) is a nanomaterial widely used in biomedicine, but its toxicity can not be ignored. In this study, the effect of GO on the blood system (the hemolysis rate, the fragility of erythrocyte, and acetylcholinesterase activity) was systematically investigated. The results showed that the hemolysis rate of erythrocytes was lower than 8% when the GO concentration was below 100 μg/mL (P<0.01). GO at low concentration levels (<5 μg/mL) had no significant effect on the fragility of erythrocytes, but GO at high concentration (10 μg/mL) increased the fragility of erythrocytes (P=0.01). Moreover, GO increased the activity of acetylcholinesterase on erythrocytes. The concentration of 20 μg/mL graphene oxide with the size >5 μm (LGO) increased the activity of acetylcholinesterase by 42.67% (P<0.05). Then molecular dynamics simulation was used to study how GO interacted with acetylcholinesterase and increased its activity. The results showed that GO was attached to the cell membrane, thus may provide an electronegative environment that helps the hydrolysate to detach from the active sites more quickly so as to enhance the activity of acetylcholinesterase.