Posselt A M, Cowan B E, Kwong L K, Vreman H J, Stevenson D K
J Pediatr Gastroenterol Nutr. 1985 Aug;4(4):650-4. doi: 10.1097/00005176-198508000-00027.
This study evaluated the efficacy of tin protoporphyrin (TP), a competitive inhibitor of heme oxygenase, in suppressing the total body excretion rate of carbon monoxide (CO), an index of total bilirubin formation, in neonatal rats with artificially created hematomas. Wistar rat litters less than 12 h old were each divided into three groups of similar weight and treated as follows: (a) saline control (S); (b) hematoma, 80 microliter blood (H); (c) TP, 65 mumol/kg, and hematoma (TP-H). CO excretion of the H group increased rapidly after hematoma formation, reaching a maximum value of 79 +/- 4 SE microliter/kg/h 25 h later. Treatment with TP did not affect the pattern of CO excretion or its magnitude (78 +/- 2 SE microliter/kg/h, 25 h posthematoma). The S group showed no increase in CO excretion at this time (40 +/- 2 SE microliter/kg/h). At the conclusion of the experiment (45 h posthematoma), the plasma total bilirubin levels were slightly lower in the TP-H rats (1.0 +/- 0.1 SE mg/dl) than in H rats (1.2 +/- 0.1 SE mg/dl). The S rats had a plasma total bilirubin concentration of 0.8 +/- 0.1 SE mg/dl. The hepatic and splenic heme oxygenase activities were decreased by 61% (p less than 0.001) and 48% (p less than 0.05), respectively, in the TP-H rats as compared to the H rats. The S and H rats had similar enzyme activities. The results of this study suggest that though single-dose TP decreased tissue heme oxygenase activity, it did not significantly affect total bilirubin formation.
本研究评估了血红素加氧酶竞争性抑制剂锡原卟啉(TP)对人工制造血肿的新生大鼠体内一氧化碳(CO)总体排泄率的抑制效果,CO总体排泄率是总胆红素生成的一个指标。将出生不到12小时的Wistar大鼠幼崽每组按体重相近分为三组,并进行如下处理:(a)生理盐水对照组(S);(b)血肿组,注射80微升血液(H);(c)TP组,65微摩尔/千克TP加血肿(TP-H)。血肿形成后,H组的CO排泄迅速增加,25小时后达到最大值79±4 SE微升/千克/小时。TP处理并未影响CO排泄的模式或其幅度(血肿形成后25小时为78±2 SE微升/千克/小时)。此时S组的CO排泄未增加(40±2 SE微升/千克/小时)。在实验结束时(血肿形成后45小时),TP-H组大鼠的血浆总胆红素水平(1.0±0.1 SE毫克/分升)略低于H组大鼠(1.2±0.1 SE毫克/分升)。S组大鼠的血浆总胆红素浓度为0.8±0.1 SE毫克/分升。与H组大鼠相比,TP-H组大鼠肝脏和脾脏的血红素加氧酶活性分别降低了61%(p<0.001)和48%(p<0.05)。S组和H组大鼠的酶活性相似。本研究结果表明,尽管单剂量TP降低了组织血红素加氧酶活性,但它并未显著影响总胆红素的生成。