黄酮衍生物对大鼠体内甲状腺素结合前白蛋白的选择性竞争结合

合成的黄酮衍生物EMD_(21388)是T_4与甲状腺素结合前白蛋白(Thyroxine-bindingprealbumin,TBPA)结合的强烈抑制物。对大鼠全身使用EMD_(21388)后,血清TBPA与T_4结合即遭抑制,而白蛋白与T_4结合则增加,因而产生血清总T_4浓度降低,游离T_4百分率(FT_4％)增加以及血清TSH降低。提示在T_4与TBPA结合受抑,并与白蛋白结合增多的同时,由于血清T_4结合蛋白结合容量的减少,血清FT_4有短暂的增加;以及EMD_21388并不能通过血脑屏障。本文也进一步表明血清FT_4的稳定是垂体-甲状腺轴功能正常的十分重要的标志,以及大鼠血清游离甲状腺素的半衰期短于1h。

SELECTIVE AND COMPETITVE IN VIVO BINDING OF FLAVONOID EMD21388 TO SERUM TRANSTHYRETIN IN THE RAT

EMD21388. a synthetic flavonoid, is a potent inhibitor of the binding of T-4 to serum thyroxine-binding pre-albumin (TBPA) both in vitro and an woo. After baing administered to rats, it inhibited the binding of T-4 to serum TBPA within Jh, and increased the binding of T-4 to albumin, resulting in a decrease in the serum T-4 concentration, an increase in the percentage of serum free T-4 and a decrease in serum TSH during a period of, at least, 4h. Since EMD21388 administration to hypothyroid rats did not affect either serum or pituitary TSH concentrations, it is possible that the decrease in serum TSH reflected a rapid inhibition of TSH secretion due to an increase in serum free T-4 secondary to a decrease in the binding capioity of serum thyroid hormone binding protein, which occured much earlier than 1h after it was administered, and a transient increased availability of the hormone to pituatary. At the same time, it seems that EMD21388 can not directly get access to the pituitary through the bloodcerebral barrier at the dosage administered.The observations also suggest that the normal range of serum free T-4 concentration is an extremely useful index to indicate normal functioning of the pituitary-thyroid axis and that the half- life of serum free T-4 in the rat is shorter than 1h.