Neurochemical and histochemical studies on the mechanism and prevention of cerebellar under-development due to perinatal hyperbilirubinemia

已知黄疸纯合子（j/j） Gunn大鼠小脑发育不全是由新生儿高胆红素血症引起的。前内侧小叶发育不良更为严重，后小叶发育不良更少。组织化学观察表明，前内侧小叶浦肯野细胞酸性强于后外侧小叶，对胆红素敏感的前内侧小叶浦肯野细胞结合胆红素的量大于对胆红素耐受的后内侧小叶浦肯野细胞。锡-原卟啉（SnPP）是一种强大的血红素加氧酶竞争性抑制剂，目前用于黄疸患者的临床试验。给j/j大鼠新生儿腹腔或皮下注射SnPP可使血清胆红素水平迅速下降，明显降低死亡率，从而防止小脑发育不全。然而，出乎意料的是，j/j大鼠的小脑发育不全没有明显改善。SnPP联合光照射致小鼠死亡，死亡率高；到20岁时，超过一半的婴儿在治疗后4小时死亡

It is known that the cerebellar hypoplasia of jaundiced homozygous (j/j) Gunn rats is caused by neonatal hyperbilirubinemia. The hypoplasia is more severely exhibited in the antero-medial lobules and even less in the posterior lobules. The histochemical observations showed that Purkinje cells in the antero-medial lobules were more acidic than the posterior, and that a larger quantity of bilirubin was bound to purkinje cells in the former which is sensitive to bilirubin than in the latter which is tolerant to the pigment.Tin-protoporphyrin (SnPP) is a powerful competitive inhibitor of the heme oxygenase and is now tested clinically for jaundiced patient. Intraperitoneal or subcutaneous administration of SnPP to j/j rat neonates caused a rapid decrease of the serum bilirubin level, an apparent reduction of the mortality rate and hence protection against the cerebellar hypoplasia. Unexpectedly, however, the cerebellar underdevelopment of j/j rats was not so markedly improved. The combination of SnPP treatment and photoirradiation induced death with a high mortality; more than half of the infants were dead 4h after treatment by 20