摘要
有研究表明，纳洛酮对内毒素引起的脑组织损害、微循环障碍、心肌缺血、呼吸功能障碍、肠黏膜病变和代谢异常等有保护作用，其机制可能和内啡肽及炎症介质有关。但尚未见纳洛酮对炎症介质和微循环影响的详细报道。本实验观察大鼠的血液炎性介质、脑组织病理和肠系膜微循环变化，及纳洛酮对内毒素血症病理变化的影响，以探讨纳洛酮在内毒素血症中发挥的保护作用。
Objective Naloxone has protective effects on some abnormalities such as brain damage, microcirculation disorder, myocardial ischemia, respiratory dysfunction, damage of intestines mucous membrane and metabolic abnormity. The mechanism of these effects may relate to endorphin and inflammatory mediators. But the reports about naloxone on brain inflammatory mediators and mesenteric microcirculation are not available. Our study was designed to investigate the protective effect of naloxone on the rats with endotoxicemia, and explore the mechanism of this drug in three aspects： inflammatory mediators, brain tissue and mesenteric microcirculation in rats.Methods A rat model of endotoxicemia was established by injection of LPS with a dose of 5 mg/kg into thigh vein. The 80 SD rats were randomly divided into four groups： Control group, Endotoxin group, Naloxone ＋Endotoxin group and Dexamethasone ＋ Endotoxin group, each group included 20 rats which were subdivided into 4 temporal subgroups （1h, 2h, 4h, 6h respectively）. The mesenteric microcirculation of rats, white blood cell and arterial gas analysis, concentration of TNF-α,IL-1β,IL-6 in serum and brain homogenate were ivstigated. Furthermore, the brain tissue pathological changes were examined.Results 1）In endotoxin group, the blood white cell of rats decreased severely, getting its bottom at 4 h, and increased at 6 h. PaO2 dropped progressively and reached its bottom at 6 h. Two hours after the injection of endotoxin,pH gained its minimum while PaCO2 peaked.2）In endotoxin group, serum TNF-α and IL-6 peaked at 2 h, IL-1 peaked at 4 h. Inflammatory mediators in brain homogenate did not parallel with those in serum.3）Brain tissue pathological changes in endotoxin group were wide halo around neuron and micro vas, decreased size of neuron, red stained cytoplasm, lost Nissl body, cell nucleus rigidity, nucleolus disappear and matrix edema.The changes got serious as time went by. 4）Endotoxin caused abnormal blood flow states, lower blood flow velocitya and fewer disparked capillary vessels, and leucocytes were stuck to vessel wall. In serious cases, blooding, embolism or even atrophy in micro vas were seen.5）At the point of 2 h, naloxone attenuate the changes of PaCO2 and pH caused by endotoxin. It apparently increased PO2 at 4 h and decreased serum IL-1 ,IL-6 at 1 h and 2 h. Rats of naloxone group had higher serum TNF-α than control group at 1 h, their brain tissue pathological changes were gentler at 1 h and 2 h. 6）Dexamethasone decreased PaCO2 at 2 h and attenuate serum changes of serum TNF-α,IL-1 ,IL-6 and brain tissue pathology at 4 h or so. Conclusion 1 ） White blood cell decreased early after endotoxin, which tallied with our result in microcirculation such as leucocytes were stuck to vessel wall and wandering out. 2）In endotoxicemia, inflammatory mediators in serum don＇t parallel with those in brain, which indicates cortical inner mediators may contribute to the mechanism at some degree. 3）Naloxone can affect serum and cortical inflammatory mediators, which indicates that it has protective effect on endotoxicemia .This kind of effect emerges at 1 h and 2 h after endotoxin and parallel with the pharmacokinetics character of naloxone. 4）Dexamethasone has protective effect on endotoxicemia also, it can partly ameliorate arterial gas and microcirculation, but it has different characters with naloxone.
出处
《世界急危重病医学杂志》
2006年第2期1178-1179,共2页
internationl journal of emergency and critical care medicine
