Levine J J, Pettei M J
Department of Pediatric Gastroenterology/Nutrition, Schneider Children's Hospital, Albert Einstein College of Medicine, New Hyde Park, N.Y.
Biol Neonate. 1991;60(3-4):230-5. doi: 10.1159/000243413.
Previous studies have demonstrated increased intestinal trypsin uptake in newborn rats compared to adults. The mechanisms that protect tissues against proteolytic damage by trypsin include trypsin-inhibitor binding and subsequent liver uptake. In order to examine these mechanisms, bovine trypsin (1.25 mg/100 g body weight) plus trace 125I-trypsin were injected into the portal vein of 2-week-old and adult rats. Liver, kidney and plasma 125I activity were assessed at 1, 5 or 15 min following infusion and the different trypsin inhibitor fractions were separated and examined for 125I activity. Newborn rats had significantly increased plasma levels of 125I-trypsin and significantly decreased liver 125I levels 1 min after infusion compared to adults. In addition, the slow decline in liver 125I activity seen in the adult rats did not occur in the newborns. The pattern of trypsin-inhibitor binding was not significantly different at 1, 5 and 15 min and there were no differences at these time intervals between newborns and adults. We suggest that the newborn liver is less effective in clearing infused trypsin leading to increased plasma levels, and this increased plasma trypsin concentration subsequently leads to increased liver levels of 125I-trypsin. The increased trypsin levels in the liver may predispose newborns to protease-induced liver damage.
先前的研究表明,与成年大鼠相比,新生大鼠肠道对胰蛋白酶的摄取增加。保护组织免受胰蛋白酶蛋白水解损伤的机制包括胰蛋白酶抑制剂结合及随后的肝脏摄取。为了研究这些机制,将牛胰蛋白酶(1.25毫克/100克体重)加微量125I标记的胰蛋白酶注入2周龄和成年大鼠的门静脉。在输注后1、5或15分钟评估肝脏、肾脏和血浆中的125I活性,并分离不同的胰蛋白酶抑制剂组分,检测其125I活性。与成年大鼠相比,新生大鼠在输注后1分钟时血浆中125I标记的胰蛋白酶水平显著升高,肝脏中125I水平显著降低。此外,成年大鼠肝脏中125I活性缓慢下降的情况在新生大鼠中未出现。胰蛋白酶抑制剂结合模式在1、5和15分钟时无显著差异,新生大鼠和成年大鼠在这些时间间隔也无差异。我们认为,新生大鼠肝脏清除输注的胰蛋白酶的效率较低,导致血浆水平升高,而这种血浆胰蛋白酶浓度的升高随后导致肝脏中125I标记的胰蛋白酶水平升高。肝脏中胰蛋白酶水平的升高可能使新生大鼠易患蛋白酶诱导的肝损伤。