Kim C B, Hintz S R, Vreman H J, Stevenson D K
Department of Pediatrics, Stanford University School of Medicine, Calif.
Dev Pharmacol Ther. 1988;11(3):166-72. doi: 10.1159/000457684.
Single subcutaneous doses (25 mumol/kg body weight) of tin-protoporphyrin (TP), a potent competitive inhibitor or heme oxygenase (HO), were administered to both suckling and adult Wistar rats. The effect of TP on the carbon monoxide excretion rate (VeCO), an index of total bilirubin formation, and on in vitro carbon monoxide (CO) production by the small intestine were evaluated. Whereas the VeCO of the adult group was decreased (p less than 0.0005) after TP, that of the suckling rat was unchanged. Gradients of CO production along the small intestine were observed in sucklings as well as adults; however, these gradients were in opposite directions. Intestinal CO production was greatest in the adult duodenum, decreasing distally; conversely, the CO production was greatest in the suckling ileum, decreasing proximally. No significant difference in CO production between control and TP-treated adult intestinal mucosa was observed. In sucklings, a significant reduction of intestinal CO production in the TP-treated rats was detected in the duodenum only (p less than 0.05). The results suggest that suckling rats differ from adults in terms of the capacity to produce CO and the direction of the gradient of CO production along the intestine. We conclude that (1) TP may not substantially decrease the in vivo production of CO by the small intestine at a dose which inhibits hepatic and splenic heme oxygenase, and (2) because after a heme load, heme is excreted into the intestine after TP administration, heme-degrading, CO-producing processes in the intestine may contribute to an animal's VeCO under such conditions.
给哺乳和成年Wistar大鼠单次皮下注射锡原卟啉（TP，一种有效的血红素加氧酶（HO）竞争性抑制剂），剂量为25 μmol/kg体重。评估了TP对作为总胆红素形成指标的一氧化碳排泄率（VeCO）以及对小肠体外一氧化碳（CO）生成的影响。TP处理后，成年组的VeCO降低（p < 0.0005），而哺乳大鼠的VeCO未改变。在哺乳大鼠和成年大鼠中均观察到沿小肠的CO生成梯度；然而，这些梯度方向相反。成年大鼠十二指肠的肠道CO生成最大，向远端递减；相反，哺乳大鼠回肠的CO生成最大，向近端递减。在对照和TP处理的成年肠黏膜之间未观察到CO生成的显著差异。在哺乳大鼠中，仅在十二指肠检测到TP处理组大鼠的肠道CO生成显著降低（p < 0.05）。结果表明，哺乳大鼠在产生CO的能力以及沿肠道的CO生成梯度方向方面与成年大鼠不同。我们得出结论：（1）在抑制肝脏和脾脏血红素加氧酶的剂量下，TP可能不会显著降低小肠体内CO的生成；（2）因为在给予血红素负荷后，TP给药后血红素会排泄到肠道中，在这种情况下，肠道中血红素降解、产生CO的过程可能会对动物的VeCO产生影响。
