Jaworek J, Konturek S J, Macko M, Kot M, Szklarczyk J, Leja-Szpak A, Nawrot-Porabka K, Stachura J, Tomaszewska R, Siwicki A, Pawlik W W
Dept. of Medical Physiology Faculty of Health Care, Medical Faculty Jagiellonian University School of Medicine, Cracow, Poland.
J Physiol Pharmacol. 2007 Mar;58(1):131-47.
Bacterial endotoxin (lipopolysaccharide, LPS), at high concentration is responsible for sepsis, and neonatal mortality, however low concentration of LPS protected the pancreas against acute damage. The aim of this study was to investigate the effect of exposition of suckling rats to LPS on the course of acute pancreatitis at adult age. Suckling rat (30-40g) received intraperitoneal (i.p.) injection of saline (control) or LPS from Escherichia coli or Salmonella typhi (5, 10 or 15 mg/kg-day) during 5 consecutive days. Two months later these rats have been subjected to i.p. cearulein infusion (25 microg/kg) to produce caerulein-induced pancreatitis (CIP). The following parameters were tested: pancreatic weight and morphology, plasma amylase and lipase activities, interleukin 1beta (IL-1 beta), interleukin 6 (IL-6), and interleukin 10 (IL-10) plasma concentrations. Pancreatic concentration of superoxide dismutase (SOD) and lipid peroxidation products; malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) have been also measured. Caerulein infusion produced CIP in all animals tested, that was confirmed by histological examination. In the rats, which have been subjected in the neonatal period of life to LPS at doses 10 or 15 mg/kg-day x 5 days, all manifestations of CIP have been reduced. In these animals acute inflammatory infiltration of pancreatic tissue and pancreatic cell vacuolization have been significantly diminished. Also pancreatic weight, plasma lipase and alpha-amylase activities, as well as plasma concentrations of IL-1beta and IL-6 have been markedly decreased, whereas plasma anti-inflammatory IL-10 concentration was significantly increased in these animals as compared to the control rats, subjected in the infancy to saline injection instead of LPS. Caerulein-induced fall in pancreatic SOD concentration was reversed and accompanied by significant reduction of MDA + 4 HNE in the pancreatic tissue. The effects of LPS derived from E. coli or S. typhi were similar. Pretreatment of suckling rats with LPS at dose of 10 mg/kg-day x 5 days resulted in the most prominent attenuation of acute pancreatitis at adult age, whereas LPS at dose of 5 mg/kg-day x 5 days given to the neonatal rats failed to affect significantly acute pancreatitis induced in these animals 2 months later. We conclude that: 1/ Prolonged exposition of suckling rats to bacterial endotoxin attenuated acute pancreatitis induced in these animals at adult age. 2/ This effect could be related to the increased concentration of antioxidative enzyme SO in the pancreatic tissue and to the modulation of cytokines production in these animals.
细菌内毒素（脂多糖，LPS），高浓度时会导致败血症和新生儿死亡，然而低浓度的LPS可保护胰腺免受急性损伤。本研究的目的是调查哺乳期大鼠接触LPS对成年期急性胰腺炎病程的影响。哺乳期大鼠（30 - 40克）连续5天腹腔内（i.p.）注射生理盐水（对照）或大肠杆菌或伤寒沙门氏菌的LPS（5、10或15毫克/千克·天）。两个月后，对这些大鼠进行腹腔内注射蛙皮素（25微克/千克）以诱发蛙皮素诱导的胰腺炎（CIP）。检测了以下参数：胰腺重量和形态、血浆淀粉酶和脂肪酶活性、白细胞介素1β（IL - 1β）、白细胞介素6（IL - 6）和白细胞介素10（IL - 10）血浆浓度。还测量了胰腺中超氧化物歧化酶（SOD）浓度以及脂质过氧化产物；丙二醛（MDA）和4 - 羟基壬烯醛（4 - HNE）。蛙皮素注射在所有受试动物中诱发了CIP，这通过组织学检查得到证实。在新生期接受10或15毫克/千克·天×5天剂量LPS的大鼠中，CIP的所有表现均减轻。在这些动物中，胰腺组织的急性炎症浸润和胰腺细胞空泡化明显减少。此外，胰腺重量、血浆脂肪酶和α -淀粉酶活性以及血浆中IL - 1β和IL - 6的浓度也显著降低，而与在婴儿期接受生理盐水注射而非LPS的对照大鼠相比，这些动物血浆中抗炎性IL - 10浓度显著升高。蛙皮素诱导的胰腺SOD浓度下降得到逆转，并伴有胰腺组织中MDA + 4 HNE的显著减少。大肠杆菌或伤寒沙门氏菌来源的LPS的作用相似。以10毫克/千克·天×5天的剂量对哺乳期大鼠进行LPS预处理，导致成年期急性胰腺炎的减轻最为显著，而以5毫克/千克·天×5天的剂量给新生大鼠注射LPS未能显著影响2个月后这些动物诱发的急性胰腺炎。我们得出以下结论：1/哺乳期大鼠长期接触细菌内毒素可减轻成年期这些动物诱发的急性胰腺炎。2/这种作用可能与胰腺组织中抗氧化酶SO浓度的增加以及这些动物细胞因子产生的调节有关。
