Rozenfeld R A, Liu X, DePlaen I, Hsueh W
Department of Pediatrics, Children's Memorial Hospital, Northwestern University Medical School, Chicago, Illinois 60614, USA.
Am J Physiol Gastrointest Liver Physiol. 2001 Oct;281(4):G957-63. doi: 10.1152/ajpgi.2001.281.4.G957.
We previously showed that group II phospholipase A2 (PLA2-II), a secretory, bactericidal, and proinflammatory protein in intestinal crypts, is upregulated after lipopolysaccharide (LPS) and platelet-activating factor (PAF) challenge. Here we examined whether germ-free environment (GF) or antibiotic treatment (ABX) affects the pathophysiological responses and intestinal PLA2-II activity after PAF (1.5 microg/kg) or LPS (8 mg/kg) injection. We found that LPS and PAF induced hypotension and mild intestinal injury in conventionally fed (CN) rats; these changes were milder in ABX rats, whereas GF rats showed no intestinal injury. PLA2-II enzyme activity was detected in normal rat small intestine; the basal level was not diminished in ABX or GF rats. PAF and LPS caused an increase in PLA2-II activity, which was abrogated in GF and ABX rats. Recolonization of GF rats by enteral contamination restituted their PLA2-II response to PAF and LPS and susceptibility to bowel injury. We conclude that PAF- and LPS-induced increases in PLA2-II activity are dependent on gut bacteria, and ABX and GF rats are less susceptible to LPS-induced injury than CN rats.
我们之前发现，Ⅱ型磷脂酶A2（PLA2-II）是一种存在于肠隐窝中的分泌性、杀菌性及促炎蛋白，在脂多糖（LPS）和血小板活化因子（PAF）刺激后会上调。在此，我们研究了无菌环境（GF）或抗生素治疗（ABX）是否会影响PAF（1.5微克/千克）或LPS（8毫克/千克）注射后大鼠的病理生理反应及肠道PLA2-II活性。我们发现，LPS和PAF在常规饲养（CN）大鼠中会诱导低血压及轻度肠道损伤；这些变化在ABX大鼠中较轻，而GF大鼠未出现肠道损伤。在正常大鼠小肠中检测到了PLA2-II酶活性；ABX或GF大鼠的基础水平未降低。PAF和LPS导致PLA2-II活性增加，而在GF和ABX大鼠中这种增加被消除。通过肠道污染对GF大鼠进行重新定殖恢复了它们对PAF和LPS的PLA2-II反应以及对肠道损伤的易感性。我们得出结论，PAF和LPS诱导的PLA2-II活性增加依赖于肠道细菌，并且ABX和GF大鼠比CN大鼠对LPS诱导的损伤更不易感。
