CdTe/ZnSQDs在小鼠肾脏中的药代动力学特征

Pharmacokinetic Characteristics of Cd Te/Zn SQDs in Kidney of the Mice

为了解Cd Te/Zn SQDs(Cd Te/Zn S量子点)在小鼠肾脏中的药代动力学特征,选择雄性ICR(Institute of Cancer Research)小鼠为动物模型,每只单次尾静脉注射5 nmol的Cd Te/Zn SQDs(粒径约为6 nm,最大发射波长590 nm)。在尾静脉注射Cd Te/Zn SQDs 15 min、1 h、6 h、24 h、72 h、168 h、2 w、4 w和6 w时剖取小鼠的肾脏,消化后使用电感耦合等离子体质谱(ICP-MS)检测其中的Cd(镉)和Te(碲)含量,Cd和Te在小鼠肾脏中浓度随时间的变化均呈现先增加后降低的趋势,Cd和Te含量分别在168 h和72 h时达到峰值(60.42±8.85)ng·g^(-1)和(18.69±0.97)ng·g^(-1),之后逐渐下降,将二者的含量以摩尔比表示,随着给药时间的延长,摩尔(Cd):摩尔(Te)由2.71:1逐渐变成1.39:1。利用3P87计算Cd和Te在肾脏中的药代动力学参数,结果发现Cd和Te在肾脏中的Vd(表观分布体积)分别为(823.14±82.76)g·kg^(-1)和(686.28±53.13)g·kg^(-1)(P<0.05);AUC(药物浓度-时间曲线下面积)分别为(24.48±2.52)μg·g^(-1)·h和(7.41±0.60)μg·g^(-1)·h(P<0.01);CL(清除率)分别为(0.90±0.11)g·kg^(-1)·h^(-1)和(1.02±0.13)g·kg^(-1)·h^(-1)(P>0.05);t1/2(半衰期)分别为(617.02±8.57)h和(458.21±1.85)h(P<0.01)。研究提示Cd和Te在肾脏含量的摩尔比随时间变化不同,QDs在体内发生了化学降解;二者的药代动力学参数不同,Cd在肾脏中的代谢速度明显慢于Te,游离的Cd2+可能引起肾脏毒性。

In order to understand the pharmacokinetic characteristics of Cd Te/Zn SQDs in kidney, male ICR micewere intravenously given a single dose（5 nmol/mouse） of Cd Te/Zn SQDs（QDs are approximately 6 nm in diameter and have maximal emission at 590 nm）. After intravenous injection, kidneys of the mice were harvested at 15 min, 1h, 6 h, 24 h, 72 h, 168 h, 2 w, 4 w and 6 w from the mice, the contents of Cd and Te in the kidney were detected by ICP-MS, The concentrations of Cd and Te changed over time in mouse kidney, with a trend to increase at first followed by a reduction. The concentration of Cd and Te reached their peak values of（60.42 ± 8.85） ng·g^（-1）and（18.69 ± 0.97） ng·g^（-1）at 168 h and 72 h respectively. With the duration of administration time, both of two indicate in the molar ratio, n（Cd）： n（Te） changes from 2.71：1 to 1.39：1 gradually. The pharmacokinetic parameters of Cd and Te in kidney were calculated. Results showed that pharmacokinetic parameters of Cd and Te in kidney were dramatically different, in which the apparent volume of distribution of Cd and Te were（823.14 ± 82.76） g·kg^（-1）and（686.28 ± 53.13） g·kg^（-1）（P〈0.05）; the area under the plasma concentration-time profiles were（24.48 ± 2.52） μg·g^（-1）·h and（7.41 ± 0.60） μg·g^（-1）·h（P 0.01）; the clearance were（0.90 ± 0.11） g·kg^（-1）·h^（-1）and（1.02 ± 0.13） g·kg^（-1）·h^（-1）（P〉0.05.）; and the half-life were（617.02 ± 8.57） h and（458.21 ± 1.85） h（P〈 0.01）, respectively. The molar ratio of Cd and Te in kidney changed over time, implying the occurrence of chemical degradation of QDs in vivo. The pharmacokinetic parameters of both elements are different, as the degradation of Cd is obviously faster than that of Te in kidney. The free Cd2 ＋may cause renal toxicity.