创伤性休克大鼠中性粒细胞CD18、糖皮质激素受体的变化及纳洛酮治疗作用的研究

Studies on expression of neutrophil CD18、glucocorticoid receptor and therapeutic effects of naloxone in traumatic shock of rats

目的 探讨中性粒细胞粘附分子ＣＤ１８（ＰＭＮＣＤ１８）、中性粒细胞糖皮质激素受体（ＰＭＮＧＲ） 在大鼠创伤性休克早期的动态变化及盐酸纳洛酮（ＮＬＸ）的治疗作用。方法 动物模型采用软组织损伤加颈动脉放血法，分别采用流式细胞仪和放射配体结合法测定ＰＭＮＣＤ１８ 、ＰＭＮＧＲ 的表达值。结果 休克组休克４５ ｍｉｎＰＭＮＣＤ１８ 表达值明显增高，随后逐渐下降，但至休克７．５ ｈ 仍高于基础表达值，两者差异有非常显著性（ Ｐ＜０ ．０１） ；ＰＭＮＧＲ 随休克时间的延长逐渐下降，到复苏２ ｈ 后最显著。肝、肺组织切片发现，复苏后２ ｈ 毛细血管内有大量白细胞粘附于血管内壁，复苏后６ ｈ 减轻。治疗组复苏后２ ｈ 、４ ｈ、６ ｈ ＰＭＮＣＤ１８ 较复苏组同时相点的结果明显降低（ Ｐ＜ ０．０１） ，而ＰＭＮＧＲ 则明显升高（ Ｐ＜ ０ ．０１）；组织学检查显示治疗组复苏后毛细血管内白细胞附壁较复苏组同时相点明显减少。结论 创伤性休克及复苏时，中性粒细胞内皮细胞（ＰＭＮＥＣ）粘附明显增强，与ＰＭＮＣＤ１８ 的表达增加有关，ＰＭＮＧＲ的减数调节是ＰＭＮＣＤ１８ 表达增加的原因之一，纳洛酮（ＮＬＸ） 可通过增加ＰＭＮＧＲ 位点?

Objective To investigate the dynamic changes of neutrophil CD18 (PMN CD18) and glucocorticoid receptor (PMN GR) and protective effects of Naloxone hydrochloride (NLX) in early traumatic shock of rats. Methods Traumatic shock was induced by soft tissue injury plus blood letting from carotid artery PMN CD18 and PMN GR were measured by flow cytometry and radioligand binding assay, respectively.Results PMN CD18 increased markedly during traumatic shock especially at 45 minutes after, then decreased gradually, but remained higer than the baseline value at 7.5 hour after shock( P <0.01); PMN GR decreased gradually during prolonged shock; the above changes reached the peak at 2 hours after resuscitation. Tissue examination showed abundant leukocytes adhered to the intima of hepatic and pulmonany capillaries 2 hours after resuscitation, but decreased at 6 hours after resuscitation. PMN CD18 was reduced dramatically in NLX group compared with that of resuscitation group at the same phase ( P < 0.01), while PMN GRs were much increased in NLX group ( P <0.01); tissue examination showed less leukocytes adhered to the hepatic and pulmonary capillarles after resusciatation in NLX group.Conclusion The adhesion of PMN EC is significantly increased during traumatic shock and after resuscitation, it may be due to upregulation of PMN CD18 expression, which inturn may be due to downregulation of PMN GR, NLX can provide protective effects by inhibiting the expression of PMN CD18 and increasing the PMN GR.(Shanghai Med J, 2000,23∶19 22)