Jaworek J, Nawrot-Porabka K, Leja-Szpak A, Szklarczyk J, Macko M, Bonior J, Stachura J, Konturek S J, Pawlik W W
Department of Medical Physiology Faculty of Health Care, Chair of Physiology Medical College, Jagiellonian University, Cracow, Poland.
J Physiol Pharmacol. 2007 Jun;58(2):287-302.
Lipopolysaccharide (LPS, endotoxin) is the component of the cellular wall of Gram negative bacteria. Endotoxemia (sepsis) could produce multiorgan failure and in the early period of life LPS are responsible for the changes of metabolism and for the reduction of protein synthesis. The influence of neonatal endotoxemia on the pancreas at adults has not been investigated yet. The aim of this study was to assess the pancreatic exocrine function in the adult rats which have been subjected, in the neonatal period of life, to chronic LPS pretreatment. LPS from E. coli or S. typhi at doses of 5, 10 or 15 mg/kg-day was administered intraperitoneally (i.p.) to the suckling rats (30 g) during 5 consecutive days. Three months later these animals (300 g) were equipped with pancreato-biliary fistulae for the in vivo secretory study. Amylase release from isolated pancreatic acini obtained from these rats was also assessed. Pancreatic tissue samples were taken for histological assessment and for the determination of gene expression for CCK1 receptor by RT-PCR. Pancreatic amylase secretions stimulated by caerulein or by diversion of pancreatic-biliary juice to the exterior (DBPJ) was significantly, and dose-dependently reduced in the adult rats which have been subjected in infancy to chronic pretreatment with LPS from E. coli or S. typhi, as compared to the untreated control. In these animals basal secretion was unaffected. In the rats pretreated with LPS in the suckling period of life caerulein-induced amylase release from isolated pancreatic acini was significantly decreased, as compared to the untreated with LPS control. This was accompanied by dose-dependent reduction of mRNA signal for CCK1 receptor on pancreatic acini. Neonatal endotoxemia failed to affect significantly pancreatic morphology as well as plasma amylase level in the adult rats. We conclude that neonatal endotoxemia reduces gene expression for CCK1 receptor and could produce impairment of the exocrine pancreatic function at adult age.
脂多糖（LPS，内毒素）是革兰氏阴性菌细胞壁的组成成分。内毒素血症（败血症）可导致多器官功能衰竭，在生命早期，LPS会引起代谢变化并降低蛋白质合成。新生儿内毒素血症对成年期胰腺的影响尚未得到研究。本研究的目的是评估成年大鼠的胰腺外分泌功能，这些大鼠在生命的新生儿期接受了慢性LPS预处理。将来自大肠杆菌或伤寒沙门氏菌的LPS以5、10或15mg/kg·天的剂量连续5天腹腔内注射给乳鼠（30g）。三个月后，这些动物（300g）被安装胰胆管瘘用于体内分泌研究。还评估了从这些大鼠分离的胰腺腺泡中淀粉酶的释放。采集胰腺组织样本进行组织学评估，并通过RT-PCR测定CCK1受体的基因表达。与未处理的对照组相比，在婴儿期接受大肠杆菌或伤寒沙门氏菌LPS慢性预处理的成年大鼠中，由蛙皮素或胰胆液引流至体外（DBPJ）刺激的胰腺淀粉酶分泌显著且呈剂量依赖性降低。在这些动物中，基础分泌未受影响。与未用LPS处理的对照组相比，在生命的哺乳期用LPS预处理的大鼠中，蛙皮素诱导的分离胰腺腺泡中淀粉酶的释放显著降低。这伴随着胰腺腺泡上CCK1受体mRNA信号的剂量依赖性降低。新生儿内毒素血症未显著影响成年大鼠的胰腺形态以及血浆淀粉酶水平。我们得出结论，新生儿内毒素血症会降低CCK1受体的基因表达，并可能在成年期导致胰腺外分泌功能受损。
