放射性示踪法研究镍在大鼠体内的药动参数与镍镉联合制毒机理的研究
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摘要
本文用同位素示踪法研究了可溶解性氯化镍在大白鼠体内的吸收、残留及排泄,实验显示:血药时间浓度曲线符合二房室开放模型,吸收速率常数Ka为6.18/h,分布相半衰期T_(1/2(a)为0.79h,消除相半衰期T_(1/2(β)为40.68h,清除速率常数CL为0.42mL·kg~(-1)·h~(-1),达峰时间T(peak)为0.53h,达峰浓度C(max)为24987.75cpm/mL,表观容积分布V(d)为0.016L/Kg;镍吸收以后,排泄较快,24h粪尿排出给药量的83.26%,其中经过尿液排出54.86%,经过粪便排出28.41%。
同位素示踪法研究可溶性氯化镍不同时间在大鼠体内的分布残留,实验显示:在连续灌胃~(63)Ni-NiCl_2溶液15d以后,在所取的22种组织中毛发、下丘脑、脑垂体、小肠、结肠、胰腺等组织有较强的药物残留,心脏、肝脏、肾脏没有发现特异残留。
同位素示踪法研究镉对镍在单性别雄鼠体内组织残留,以便对镍镉联合制毒机理研究提供一些参考。实验结果显示:当雄性大鼠长期单纯的吸收镍时,除了对动物心血管组织没有影响之外,对其余组织的影响均较严重;当雄性大鼠长期接触低剂量的镍镉混合物时候,对机体的破环主要以镉中毒为主,镍只对很少组织有影响;当接触高剂量的镍镉混合物时,镍和镉均对肌体有影响。
The absorption distribution and excretion of ~(63)Ni-NiCl_2 in Rat were studied by using Liquid scintillation counting method,It was observed that the concentration-time curves in blood fitted the two dicompart-ment model of pharmacokinetics,Ka=6.18h,T_(1/2(α))=0.79h,T_(1/2(β))=40.68h,CL=0.42mL/(kg·h), T(peak)=0.53h,C(max)=14.99MBq/L,V(d)=0.016L/Kg.~(63)Ni-NiCl_2 was existed in all 12 tissues tested;at 0.25h,radioactivity in intestine were the highest,and that in stomach and fattiness were higher;at 3h,liver,stomach and intestine were higher; the germen was the least;The liver and lung was the higher at 24h.In 24h 83.26%of radioactivity of oral administration was eliminated by urine and feces,54.86%by urine,28.41%by feces.After rats were treated by ~(63)Ni-NiCl_2 for 15days,in 22 tissues tested,the hair,hypothalamus,hypothesis,pancreas,small and large intestines were higher,and the residual medicine of ~(63)Ni-NiCl_2 wasn't discovered in liver,kidney and heart.
Effects of CdCl_2 on tissue residual medicine of ~(63)Ni-NiCl_2 in Rats has been studied by isotope tracer,the experiment showed that ~(63)Ni-NiCl_2 has been found in 19 tissues tested in whole 22 tissues after infusing in stomach for 8d and lacking of food and water for 72h with 0mg/kg·bwCdCl_2+8.76MBq/kg·bw~(63)Ni-NiCl_2;After the same method with 0.5mg/kg·bwCdCl_2+8.76MBq/kg·bw~(63)Ni-NiCl_2,the result showed that the 7 tissues of all 21 tissues had some counts.
After the above method with 1mg/kg·bwCdCl_2+8.76MBq/kg·bw~(63)Ni-NiCl_2,the result showed that only 2 tissues had counts,others weren't found.And after infusing in stomach for 8d and lacking of food and water for 72h with 10mg/kg·bwCdCl_2+8.76MBq/kg·bw~(63)Ni-NiCl_2,the count has been tested in 7 tissues,bone,eyeball,hair and so on.after infusing in stomach with 10mg/kg·bwCdCl_2+8.76MBq/kg·bw~(63)Ni-NiCl_2,11 tissues tested had counts.
同位素示踪法研究可溶性氯化镍不同时间在大鼠体内的分布残留,实验显示:在连续灌胃~(63)Ni-NiCl_2溶液15d以后,在所取的22种组织中毛发、下丘脑、脑垂体、小肠、结肠、胰腺等组织有较强的药物残留,心脏、肝脏、肾脏没有发现特异残留。
同位素示踪法研究镉对镍在单性别雄鼠体内组织残留,以便对镍镉联合制毒机理研究提供一些参考。实验结果显示:当雄性大鼠长期单纯的吸收镍时,除了对动物心血管组织没有影响之外,对其余组织的影响均较严重;当雄性大鼠长期接触低剂量的镍镉混合物时候,对机体的破环主要以镉中毒为主,镍只对很少组织有影响;当接触高剂量的镍镉混合物时,镍和镉均对肌体有影响。
The absorption distribution and excretion of ~(63)Ni-NiCl_2 in Rat were studied by using Liquid scintillation counting method,It was observed that the concentration-time curves in blood fitted the two dicompart-ment model of pharmacokinetics,Ka=6.18h,T_(1/2(α))=0.79h,T_(1/2(β))=40.68h,CL=0.42mL/(kg·h), T(peak)=0.53h,C(max)=14.99MBq/L,V(d)=0.016L/Kg.~(63)Ni-NiCl_2 was existed in all 12 tissues tested;at 0.25h,radioactivity in intestine were the highest,and that in stomach and fattiness were higher;at 3h,liver,stomach and intestine were higher; the germen was the least;The liver and lung was the higher at 24h.In 24h 83.26%of radioactivity of oral administration was eliminated by urine and feces,54.86%by urine,28.41%by feces.After rats were treated by ~(63)Ni-NiCl_2 for 15days,in 22 tissues tested,the hair,hypothalamus,hypothesis,pancreas,small and large intestines were higher,and the residual medicine of ~(63)Ni-NiCl_2 wasn't discovered in liver,kidney and heart.
Effects of CdCl_2 on tissue residual medicine of ~(63)Ni-NiCl_2 in Rats has been studied by isotope tracer,the experiment showed that ~(63)Ni-NiCl_2 has been found in 19 tissues tested in whole 22 tissues after infusing in stomach for 8d and lacking of food and water for 72h with 0mg/kg·bwCdCl_2+8.76MBq/kg·bw~(63)Ni-NiCl_2;After the same method with 0.5mg/kg·bwCdCl_2+8.76MBq/kg·bw~(63)Ni-NiCl_2,the result showed that the 7 tissues of all 21 tissues had some counts.
After the above method with 1mg/kg·bwCdCl_2+8.76MBq/kg·bw~(63)Ni-NiCl_2,the result showed that only 2 tissues had counts,others weren't found.And after infusing in stomach for 8d and lacking of food and water for 72h with 10mg/kg·bwCdCl_2+8.76MBq/kg·bw~(63)Ni-NiCl_2,the count has been tested in 7 tissues,bone,eyeball,hair and so on.after infusing in stomach with 10mg/kg·bwCdCl_2+8.76MBq/kg·bw~(63)Ni-NiCl_2,11 tissues tested had counts.
引文
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