盐酸纳美芬对大鼠创伤性脑损伤后炎症反应的影响  

Impact of nalmefene hydrochloride on inflammatory reaction in rats with traumatic brain injury

作　　者：张永[1] 高培龙[2] 褚沛[1] 闵光宁[1] 滕永军[1] 王文进[1] 杨兴华[1] 

机构地区：[1]兰州大学第一医院急诊创伤外科,730030 [2]武警医学院附属医院脑系中心神经外三科

出　　处：《中华创伤杂志》2013年第10期991-995,共5页Chinese Journal of Trauma

基　　金：甘肃省科技厅基金资助项目（1004TCYA026）

摘　　要：目的观察不同剂量盐酸纳美芬（nalmefe nehydrochloride，NAL）治疗创伤性脑损伤（traumatic brainin jury，TBI）后TNF-α及NF-kB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，0．2ms／kg）组（TBI＋NAL，组）、TBI＋中剂量NAL（腹腔注射，0．14mg／kg）组（TBI＋NAL2组）、TBI＋低剂量NAL（腹腔注射，0．07ms／κg）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-α及NF-kBmRNA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＋NALl、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-kB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-kB的增加（P〈0．05），其中TBI＋NAL：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-KB 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 ＋ NAL1 group）, 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-KB 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 ＋ NAL3 group, with especially obvious improvement in TBI ＋ NAL2 group. In PCR assay, significant expression of NF-KB and TNF-ct 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.

关 键 词：脑损伤 盐酸纳美芬 肿瘤坏死因子-Α 核因子-KB 

分 类 号：R651.15[医药卫生—外科学]