三甲基氯化锡在SD大鼠体内的吸收、分布、排泄研究

The absorption,distribution and excretion of TMT in SD rats

目的探讨三甲基氯化锡（TMT）的吸收、分布、排泄规律。方法取SD大鼠108只，雌雄各半，随机分为18组，每组雌雄各3只。第1组为空白对照组，生理盐水灌胃后立即眼眶采血，第2—18组灌胃给予TMT10ms／kg，分别在染毒后10min、20min、30min、1h、2h、3h、4h、6h、8h、12h、24h、3d、6d、9d、12d、28d、90d共17个时间点经眼眶采血并采集主要脏器。另取SD大鼠10只，灌胃给予TMT10mg／kg，收集染毒前连续12h及染毒后第1、2、3、6、9、12、18、28、40、55、70、90天共13个时间段连续24h的尿液。用GC-MS测定血液、组织、尿液中TMT的含量，用3P87软件计算毒代参数。结果（1）吸收：大鼠灌胃TMT后，全血和血浆半吸收期分别为0．16h和0．21h；清除率分别为1．77×10^-4L／（kg·h）和0．03L／（kg·h）；消除半减期分别为15d和10d。（2）分布：灌胃后10min组织中即可检测到TMT，6h达到峰值；红细胞中TMT浓度远高于各主要脏器，且红细胞〉脾〉肝〉肾〉心。TMT在组织中消除半减期为10d，RBC达16．53d。（3）排泄：TMT经尿液排泄较缓慢，尿TMT第6天最高，第90天仍可检测到TMT。结论大鼠灌胃给予TMT染毒后，TMT可被快速吸收，迅速分布在红细胞内，可通过血脑屏障进入脑，缓慢经尿排出。

Objective To study the metabolic pattern of trimethyltin chloride （TMT） in rats, including absorption, dis tribution and excretion. Methods SD rats （54 females and 54 males） were divided into 18 groups randomly （3 males and 3 females for each group）. The 1st group was control group, their blood samples were immediately taken from orbital vien plexus after intraperitoneal （ip） injection of normal saline. The other 17 groups were ip given TMT 10 mg/kg, the blood samples were collected atl0min, 20rain, 30rain, 1 h, 2h, 3 h, 4h, 6h, 8 h, 12h, 24hand3 d, 6d, 9d, 12d, 28 d, 90d later after injection respectively from orbital vein plexus; the main organs were also taken at the same time. In another test, 5 female and 5 male rats were given TMT 10 mg/kg orally, and collected the 24 h urine samples before （ -12--0 h） and after （ 1, 2, 3, 6, 9, 12, 18, 28, 40, 55, 70 and 90 d respectively after intragastric administration） exposure. The TMT level in blood, organs and urine was detected by GC-MS. The toxicokinetic parameters were calculated using Software 3P87. Results （ 1 ） Absorption ： The half absorption time were 0. 16 h and 0. 21 h, the clearance rate were 1.77 × 10^-4 L/ （ kg . h） and 0.03 L/ （kg . h） and the elimination half-life of TMT were 15 days and 10 days in blood and plasma respectively. （2） Distribution： 10 inin after intragastric administration, TMT might be detected in tissues, in 6 h the peak-values could be reached. The order of TMT concentrations from the higher to lower was erythrocytes 〉 spleen 〉 liver 〉 kindney 〉 heart; the elimination halflife in tissues was 10 d, while in erythrocytes it could reached 16. 53 d. （3） Elimination： TMT excreted in urine but quite slow and relatively constant. The peak level of urinary TMT corrected by creatinine was at the 6th day, and at 28th day after exposure, it still could be detected （about 1/8 of peak level）. The TMT could still be detected in urine on the 90 th day. Conclusion The results suggested that TMT could be rapidly absorbed after intragastric administration and quickly distributed in red cell of rats, which might entered into brain through blood-brain barrier and be excreted through urine very slowly.