壬基酚在SD大鼠内分泌腺、胃、心脏、肝脏、肾脏和血清的分布与消除

Distribution and Elimination of Nony lphenol in Endocrine Glands,Stomach,Heart,Liver,Kidney and Serum of SD Rats

研究壬基酚经消化道摄入后在SD大鼠的内分泌腺、胃、心脏、肝脏、肾脏和血清中的分布与消除情况。取39只SD雄性大鼠随机分为13组(每组3只),除对照组(一次性给予同等剂量玉米油)外其余各组一次性灌胃400 mg·kg^(-1)的壬基酚,在灌胃后的0.25、0.5、1、2、4、8、12、24、48、72、96和120 h腹腔注射戊巴比妥钠麻醉处死大鼠,取其内分泌腺(胸腺、甲状腺和肾上腺)、胃、肝脏、肾脏、心脏和血清,使用高效液相色谱法检测壬基酚的含量,并计算代谢动力学相关参数。代谢动力学参数包括二室模型分布相半衰期(t_(1/2α))、曲线下面积(AUC)、自中央室向外周室转运速率常数(K_(12))、自外周室向中央室转运速率常数(K_(21))、平均驻留时间(MRT_(0-t))、二室模型清除相半衰期(t_(1/2β))、中央室总体清除率(CL/F)、自中央室消除速率常数(K_(10))、吸收相半衰期(t_(1/2)(Ka))。壬基酚在大鼠各器官组织内的代谢除肝脏外均为二室模型。在内分泌腺中,胸腺内峰浓度最大,c_(max)=4.927 mg·L^(-1),曲线下面积最大,AUC _(0-∞)=766.163 mg·L^(-1)·h、平均驻留时间最长,MRT_(0-t)=53.901 h;肾上腺组织中壬基酚二室模型清除相半衰期最长,t_(1/2β)=1306826.882 h;甲状腺组织中壬基酚的t_(1/2)(Ka)=1.375 h、K_(12)=0.275h^(-1)、K_(21)=0.165h^(-1)、MRT_(0-t)=50.705 h;在实质性器官中,胃组织中壬基酚的达峰时间最早,T_(max)=2 h,峰浓度最高,c_(max)=41.4 mg·L^(-1),曲线下面积最大,AUC _(0-∞)=364.319 mg·L^(-1)·h;心脏组织中壬基酚的T_(1/2 K a)=2.013 h,CL/F=7.228 L·kg^(-1)·h^(-1);肝脏组织中壬基酚的K_(10)=0.21h^(-1);肾脏组织中各代谢动力学参数数值与肝脏相似;血清中的各项代谢动力学参数数值均处于中等水平。壬基酚主要分布在胸腺组织和胃组织中,在胃组织中驻留时间短易被吸收,在胸腺组织中驻留时间长且浓度高。壬基酚在肝脏和肾脏中清除率高。

To study the distribution and elimination of nonylphenol(NP)in the endocrine glands,stomach,heart,liver,kidney and serum of SD rats which are exposed to NP by gavage.Thirty-nine SD male rats were randomly divided into 13 groups(n=3 per group).The rats were gavaged with NP in corn oil at dose level of 400 mg·kg^(-1) or corn oil alone(vehicle control,C)once.At 0.25,0.5,1,2,4,8,12,24,48,72,96 and 120 h after the last gavage,rats from all treatment groups were euthanized under deep anesthesia by intraperitioneal injection of pentobarbital sodium,respectively.NP concentrations in endocrine glands(i.e.,thymus,thyroid,adrenal glands),stomach,liver,kidney,heart and serum were detected using the high performance liquid chromatography(HPLC)technique.Metabolokinetic parameters,including the half-life of distribution of two-compartment model(t_(1/2α)),the half-life of elimination of two-compartment model(t_(1/2β)),area under curve(AUC),distribution rate constant from central compartment to peripheral compartment(K_(12)),distribution rate constant from peripheral compartment to central compartment(K_(21)),mean residence time(MRT_(0-t)),apparent clearance(CL/F)and elimination rate constant from the central compartment(K_(10)),absorption half-life(t_(1/2)(Ka))were assessed.The metabolism of NP in all organs and tissues of rats was corresponding to a two-compartment model rather than liver.In the endocrine glands,the maximum peak concentration(c_(max))for NP in thymus was 4.927 mg·L^(-1).The biggest(AUC _(0-∞))was 766.163 mg·L^(-1)·h,and the longest MRT_(0-t) was 53.901 h.t_(1/2β)for NP in adrenal gland was 1306826.882 h,which was longest.t_(1/2)(Ka),K_(12),K_(21) and MRT_(0-t) for NP in thyroid were 1.375 h,0.275h^(-1),0.165h^(-1) and 50.705 h,respectively.The peak time(T max),c_(max) and the biggest(AUC _(0-∞))for NP in stomach were 2 h,41.4 mg·L^(-1),364.319 mg·L^(-1)·h,respectively.t_(1/2)(Ka) and CL/F for NP in heart were 2.013 h and 7.228 L·kg^(-1)·h^(-1).K_(10) for NP in liver was 0.21h^(-1).The values of metabolokinetic parameters for NP in kidney was similar to those of the liver.The values of metabolokinetic parameters for NP in serum was at an intermediate level.NP is mainly distributed in the thymus and stomach.NP is absorbed easily in stomach with short residence time,while NP concentration is high in thymus with long residence time.NP could be eliminated in the liver and kidney with high clearance.