Kernicterus in Rats with an Inherited Deficiency of Glucuronyal Transferase

[摘要] Aside from the great theoretic interest, the experiments described in this paper have considerable practical importance in providing a means of studying the efficacy of treatments designed to prevent kernicterus. A comprehensive study of a strain of rats (the Gunn strain) which have a hereditary deficiency of the enzyme required to conjugate bilirubin, and thus develope jaundice due to increased concentration of unconjugated bilirubin in the blood and tissues. The rats developed kernicterus which was apparently identical with that seen in human beings and is the only example of kernicterus in animals that fulfills rigid criteria outlined by the authors. Extensive data on the natural history of the bilirubinemia and development of kernicterus in the rats, as determined by chemical and pathologic techniques, are provided. Bilirubin itself is incriminated as the toxic agent producing the characteristic changes in the brain in kernicterus. Sulfonamides were found to augment the toxic effects of bilirubin, apparently because of competition between bilirubin and sulfonamides for binding sites on serum albumin. Neither infection nor hypoxia appeared to aggravate the effects of bilirubin.Administration of sodium glucuronate to jaundiced rats was followed by a decrease in bilirubin in the serum which at times exceeded 50%. This was not accompanied by any postponement of the onset of signs of damage to the central nervous system and did not prevent development of kernicterus. It appeared that the decrease in bilirubin in the serum may have resulted from an increased transferral to tissues rather than elimination through renal excretion.On the basis of the knowledge of this strain of rats, it should be possible to explore the usefulness of proposed therapeutic regimens in the experimental animal without jeopardizing the course of human infants who might be successfully treated with exchange transfusion pending the discovery of a more satisfactory therapy.

[学科分类] 儿科学