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脂多糖和螯合剂对硫柳汞给药小鼠大脑中汞含量的影响。

Effects of lipopolysaccharide and chelator on mercury content in the cerebrum of thimerosal-administered mice.

机构信息

Department of Life Sciences, School of Science & Engineering, Kinki University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan.

出版信息

Environ Toxicol Pharmacol. 2007 Nov;24(3):316-20. doi: 10.1016/j.etap.2007.08.004. Epub 2007 Aug 19.

Abstract

Thimerosal is one of the best-known preservative agents for vaccines in the world but a relationship between its use and autism has long been suspected so that its effects on the brain need more detailed research. We here examined the influence of lipopolysaccharide injury to the blood-brain barrier on the penetration of mercury from thimerosal into mouse cerebrums, as well as the effect of chelator of heavy metals on cerebrum mercury content. Mercury can be expected to be detected in the cerebrum of normal mice, because the metal is present in standard mouse chow. When 60μg/kg of thimerosal was subcutaneously injected into the mouse, the mercury content in the cerebrum was significantly higher 48h after the thimerosal injection with a maximum peak after 72h. In addition, mercury content in the cerebrum was still higher on day 7 than in the control group. When lipopolysaccharide was pre-injected into mice to induce damage on blood-brain barrier, the mercury content in the cerebrum was significantly higher at 24 and 72h after the injection of 12μg/kg of thimerosal compared to the control group, this dose alone does not cause any increase. The mercury content in the cerebrums of mice was decreased to the control group level on day 7 when a chelator, dimercaprol, was administered once a day from days 3 to 6 after a 60μg/kg, s.c. injection. In addition, d-penicillamine as a chelator decreased the mercury contents in the cerebrum after the high dose administration. In conclusion, a physiological dose of thimerosal did not increase the content of mercury in the cerebrum, but levels were increased when damage to the blood-brain barrier occurred in mice injected with thimerosal. In addition, a chelator of heavy metals may be useful to remove mercury from the cerebrum.

摘要

硫柳汞是世界上最著名的疫苗防腐剂之一,但长期以来人们一直怀疑其使用与自闭症之间存在关联,因此需要对其对大脑的影响进行更详细的研究。我们在此研究了脂多糖损伤血脑屏障对硫柳汞汞进入小鼠大脑的渗透的影响,以及重金属螯合剂对大脑汞含量的影响。由于金属存在于标准的小鼠饲料中,因此可以预期在正常小鼠的大脑中检测到汞。当将 60μg/kg 的硫柳汞皮下注射到小鼠中时,在硫柳汞注射后 48 小时,大脑中的汞含量明显升高,72 小时后达到峰值。此外,在第 7 天,大脑中的汞含量仍高于对照组。当预先向小鼠注射脂多糖以诱导血脑屏障损伤时,与对照组相比,在注射 12μg/kg 硫柳汞后 24 和 72 小时,大脑中的汞含量明显更高,而单独使用该剂量不会引起任何增加。当从第 3 天到第 6 天每天给予螯合剂二巯丁二酸一次时,在 60μg/kg 皮下注射后第 7 天,小鼠大脑中的汞含量降低到对照组水平。此外,作为螯合剂的 D-青霉胺在高剂量给药后降低了大脑中的汞含量。总之,生理剂量的硫柳汞不会增加大脑中的汞含量,但当给注射了硫柳汞的小鼠造成血脑屏障损伤时,汞含量会增加。此外,重金属螯合剂可能有助于从大脑中去除汞。

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