FLIP腺病毒提升大鼠肺组织FLIP表达及其对急性肺损伤防治作用的研究  

Effects of Ad-FLIP on Expression of FLIP in Rats Lung and Its Protective Effect in Acute Lung Injury

作　　者：王文雅[1] 屈朔瑶[1] 欧阳海峰[1] 黄芸[1,2] 吴朔[1] 吴昌归[1] 

机构地区：[1]第四军医大学西京医院呼吸内科,陕西西安710032 [2]解放军第533医院,云南昆明650225

出　　处：《中国呼吸与危重监护杂志》2010年第2期158-162,共5页Chinese Journal of Respiratory and Critical Care Medicine

基　　金：全军医药卫生科研基金(编号:WS06P487)

摘　　要：目的观察Fas相关死亡域样白介素1β转换酶抑制蛋白(FLIP)重组体腺病毒滴鼻吸入对大鼠肺组织FLIP表达的影响以及对急性肺损伤(ALI)的防治效果。方法48只SD大鼠随机分为4组,每组12只。FLIP治疗组:脂多糖(LPS)腹腔注射法建立大鼠ALI模型,制模后给予Ad-FLIP腺病毒滴鼻吸入;FLIP预防组:先以Ad-FLIP腺病毒感染大鼠然后复制ALI模型。对照治疗组和对照预防组则分别在制模之后和之前,给予增强型绿色荧光蛋白(EGFP)腺病毒载体作为对照。观察各组大鼠的一般情况和肺大体标本,光镜下观察肺组织病理学改变,测定肺组织湿干重比(W/D)和肺通透性指数(LPI)。采用RT-PCR、免疫组化法检测并比较各组肺组织FLIP的表达水平。结果FLIP治疗组和预防组与各对照组相比,大鼠一般情况较好,肺大体标本和组织病理学改变减轻,肺组织湿干重比、肺通透性指数降低,肺组织FLIP的mRNA和蛋白表达水平均显著增高(P<0.01)。结论滴鼻吸入FLIP重组体腺病毒能够上调大鼠肺组织的FLIP表达,保护肺呼吸膜,减轻肺水肿,对大鼠ALI有一定防治作用。Objective To investigate the expression of FLIP in the lung of rats and the protective effect in development of acute lung injury（ALI）with the adenovirus vector carrying FLIP gene（Ad-FLIP）inhaled.Methods Forty-eight rats were randomly divided into four groups,with 12 rats in each gruop.In treatment group,ALI rats model was eatablished by LPS intraperitoneal injection and then inhaled Ad-FLIP vector.In prevention group,the animals were infected with Ad-FLIP vector before ALI model was established.Two control groups of treatment and prevention received Ad-EGFP vectors respectively.Pathological changes of lung were observed under light microscope.Wet/dry weight（W/D）of lung lobes and lung permeability index（LPI）were also measured.The mRNA and protein expressions of FLIP in lung were investigated by RT-PCR and immunohistochemistry,respectively.Results Lung histopathological changes were alleviated,the index of W/D and LPI were significantly lower,the expressions of FILP mRNA and protein in the lung were elevated both in the treatment group and prevention group compared to the control groups（all P0.01）.Conclusion Ad-FLIP transfection can up-regulate the expression of FLIP in lung of rats,and might protect respiratory membrane and lessen pulmonary edema to prevent the development of ALI.

关 键 词：急性肺损伤 Fas相关死亡域样白介素1β转换酶抑制蛋白 腺病毒 

分 类 号：R563.8[医药卫生—呼吸系统]