Shapiro S M
Department of Neurology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0211.
Pediatr Res. 1993 Nov;34(5):629-33. doi: 10.1203/00006450-199311000-00014.
Neurologic and audiologic sequelae produced by bilirubin toxicity are preventable by appropriately timed therapeutic intervention. To understand the timing and reversibility of the neural dysfunction that follows exposure to bilirubin, we recorded brainstem auditory evoked potentials (BAEP) in the Gunn rat model of bilirubin encephalopathy. Abnormal BAEP occur in jaundiced Gunn rats after injection of sulfadimethoxine (sulfa) 100 mg/kg intraperitoneally, which displaces bilirubin from blood albumin binding sites and promotes the net transfer of bilirubin into brain tissue. Reversal of BAEP abnormalities with injection of human serum albumin (HSA) 2 g/kg intraperitoneally was studied in 17- to 20-d-old jaundiced Gunn rats. One animal from each of 14 litters was randomly assigned to one of the following treatment groups: 1) sulfa alone, 2) sulfa + HSA at 2 h, 3) sulfa + HSA at 8 h, or 4) saline alone. BAEP were recorded in each rat before and 0.1, 4, 8, 24, and 48 h after injection of sulfa or saline. BAEP I-II interwave intervals increased in all sulfa groups (p < 10(-9) to 0.27 ms (21%) above baseline at 8 h for the two sulfa groups not receiving treatment before that time (p = 0.0002), but increased less for the sulfa group given HSA at 2 h compared with untreated animals (p = 0.02). Partial recovery of function occurred at 24 and 48 h for both HSA-treated groups compared with their 8-h values (p = 0.001), and there was increased mortality at 24 h for the sulfa group not treated with HSA (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
胆红素毒性所产生的神经和听力后遗症可通过适时的治疗干预加以预防。为了解胆红素暴露后神经功能障碍的发生时间及可逆性,我们在胆红素脑病的冈恩大鼠模型中记录了脑干听觉诱发电位(BAEP)。腹腔注射100 mg/kg磺胺二甲氧嘧啶(磺胺)后,黄疸型冈恩大鼠会出现异常BAEP,该药物可使胆红素从血白蛋白结合位点上解离,促进胆红素向脑组织的净转移。我们对17至20日龄的黄疸型冈恩大鼠进行研究,腹腔注射2 g/kg人血清白蛋白(HSA)后BAEP异常能否逆转。从14窝中各选取1只动物,随机分配至以下治疗组之一:1)仅用磺胺;2)磺胺 + 2小时后用HSA;3)磺胺 + 8小时后用HSA;或4)仅用生理盐水。在注射磺胺或生理盐水前以及注射后0.1、4、8、24和48小时,记录每只大鼠的BAEP。所有磺胺组的BAEP I-II波间期均增加(p < 10(-9)至0.27 ms,在8小时时,未在此之前接受治疗的两个磺胺组比基线升高21%(p = 0.0002),但与未治疗动物相比,2小时时给予HSA的磺胺组增加较少(p = 0.02)。与8小时时的值相比,两个HSA治疗组在24和48小时时功能出现部分恢复(p = 0.001),未用HSA治疗的磺胺组在24小时时死亡率增加(p < 0.001)。(摘要截短于250字)