盐酸纳美芬对大鼠创伤性脑损伤后炎症反应的影响

摘要

目的 观察不同剂量盐酸纳美芬(nalmefene hydrochloride,NAL)治疗创伤性脑损伤(traumatic brain injury,TBI)后TNF-α及NF-κB的变化,探讨NAL对大鼠TBI后炎症反应的影响及作用机制. 方法 采用改良Feeney法自由落体撞击制作大鼠TBI模型,大鼠按随机数字表法分为假手术组、TBI组、TBI+高剂量NAL(腹腔注射,0.2 mg/kg)组(TBI+ NAL1组)、TBI+中剂量NAL(腹腔注射,0.14 mg/kg)组(TBI+ NAL2组)、TBI+低剂量NAL(腹腔注射,0.07 mg/kg)组(TBI+ NAL3组).观察各组脑组织的形态学改变,采用实时定量PCR测定TNF-d及NF-κBmRNA含量. 结果 HE染色结果显示,TBI组脑实质出现严重的损伤和炎性浸润,而TBI+NAL1、TBI+ NAL2、TBI+ NAL3组损伤和炎性改变均得以改善,且TBI+ NAL2组的改善作用最为突出；实时定量PCR结果显示,TBI后1,3,5,7d,NF-κB和TNF-α的表达量均显著增加(P＜0.05),而给予NAL治疗可显著逆转TNF-α和NF-κB的增加(P＜0.05),其中TBI+ NAL2组作用最显著. 结论 NAL可减轻TBI后炎症反应,促进损伤后恢复,并且具有浓度窗口.%Objective To observe the changes of TNF-α and NF-κB after different doses of nalmefene hydrochloride (NAL) therapy for traumatic brain injury (TBI) in an effort to identify the effect of NAL on TBI-induced inflammatory response and the possible mechanism.Methods A model of TBI in the rat was produced using the improved Feeney' s free-fall impact method.The animals were randomly divided into sham group,TBI group,TBI + large dose of NAL (ip,0.2 mg/kg) group (TBI + NAL1group),TBI + medial dose of NAL (ip,0.14 mg/kg) group (TBI + NAL2 group),TBI + small dose of NAL (ip,0.07 mg/kg) group (TBI + NAL3 group).Form of brain tissues in each group was observed and mRNA levels of TNF-α and NF-κB were measured by real-time quantitative PCR assay.Results HE staining revealed severe injury and inflammatory infiltration of brain parenchyma in TBI group ;on the contrary,the situation ameliorated in TBI + NAL1 group,TBI + NAL2 group and TBI + NAL3group,with especially obvious improvement in TBI + NAL2 group.In PCR assay,significant expression of NF-κB and TNF-α was observed at post-TBI days 1,3,5 and 7 (P ＜ 0.05),followed by great reverse after NAL therapy (P ＜ 0.05),particularly in TBI + NAL2 group.Conclusions NAL can reduce the inflammation response to TBI and promote post-injury recovery.Moreover,there exists a NAL concentration window.