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目的观察硫柳汞肌肉注射在大鼠体内的长期毒性反应的性质、程度,并确认靶器官。方法先进行硫柳汞在大鼠体内的最大耐受量(MTD)实验,由此设计长期毒性实验剂量,每组24只大鼠,肌肉注射,每周给药1次,共5周,停药恢复期为2周。观测给药期间动物的一般状况,并在末次给药后1周和停药恢复两周后解剖动物,进行血液学、生物化学和病理学检测,对实验结果统计分析,确认可能的毒性反应。结果硫柳汞大剂量(30mg/kg)肌肉注射可致大鼠双下肢给药部位肌肉硬结,肢体瘫痪,体重明显减轻,于第4次给药后濒临死亡;其肝功、肾功明显异常,血液系统紊乱;肺脏、肝脏、肾脏组织结构破坏严重;中枢神经系统和坐骨神经均可见空泡变性;心肌、胰、脾、肾上腺等脏器也有不同程度的损害。随着剂量的大幅降低,硫柳汞的毒性也明显减弱,与临床使用剂量相当时未见明显毒性反应。结论硫柳汞在较高剂量给药时可出现多脏器损害,特别是对中枢和外周神经及给药部位肌肉的损害较为严重,这种毒性反应随着剂量减小而降低。
Objective To observe the nature and extent of long-term toxicity of thimerosal intramuscular injection in rats and to confirm the target organ. Methods The maximum tolerated dose (MTD) of thimerosal in rats was used to design a long-term toxic experimental dose. Twenty-four rats in each group were injected intramuscularly once a week for 5 weeks, The period is 2 weeks. The general condition of the animals during the administration was observed. One week after the last administration and two weeks after the withdrawal, the animals were dissected for hematological, biochemical and pathological examination. Statistical analysis of the experimental results confirmed possible toxic reactions. Results Thimerosal at a high dose (30mg / kg) intramuscularly induced muscular sclerosis, limb paralysis and weight loss in the lower limbs of rats. It was dying after the fourth administration. The liver function and renal function were obviously abnormal. The blood System disorders; lung, liver, kidney tissue damage serious; central nervous system and sciatic nerve vacuolar degeneration can be seen; myocardial, pancreatic, spleen, adrenal and other organs also have varying degrees of damage. Toxicity of thimerosal was significantly weakened as the dose was significantly reduced, with no apparent toxicological response at comparable doses of clinical use. Conclusions Thimerosal may cause multiple organ damage when administered at higher doses, especially for the central and peripheral nerves and the administration site. This toxicity response decreases with dose reduction.