己酮可可碱对脓毒症致急性肺损伤核因子-κB和明胶酶的干预作用  

Effect of pentoxifylline on lung nuclear factor - -κB and gelatinase expressions in mice with acute lung injury

作　　者：闫树凤[1] 朱光发[1] 张向峰[1] 靳丽妍[1] 吴春婷[1] 

机构地区：[1]首都医科大学附属北京安贞医院呼吸科,北京100029

出　　处：《中国急救医学》2012年第12期1092-1095,I0011,共5页Chinese Journal of Critical Care Medicine

基　　金：北京市教育委员会科技计划面上项目（KM200810025006）;北京市自然科学基金项目（7112039）

摘　　要：目的研究己酮可可碱（pentoxifylline，PTX）对急性肺损伤（acutelunginjury，Au）核因子-κB（nuclearfactor-κB，NF-κB）、明胶酶（gelatinase，MMP-2，MMP-9）的干预作用。方法将112只小鼠随机分为盐水对照组（NS组）、己酮可可碱对照组（PTX组）、手术组（CLP组）和己酮可可碱干预组（C＋P组）。采用盲肠结扎穿孔（cecalligationandpuncture，CLP）法复制脓毒症ALI模型，C＋P组在手术基础上尾静脉注射己酮可可碱40mg／kg干预。各组小鼠在对应时间段处死，观察肺病理改变；免疫组化染色检测肺NF-κB染色强度；逆转录-聚合酶链反应（RT-PCR）检测肺NF-κB、MMP-2、MMP-9的mRNA表达；酶联免疫吸附法（ELISA）测定支气管肺泡灌洗液（bronchoalveolarlavagefluid，BALF）中MMP-2、MMP-9的蛋白含量。结果盲肠结扎穿孑L能够引起Au。CLP组ALI病理表现明显，C＋P组较CLP组明显减轻。C＋P组肺组织NF-κB的染色强度、面积低于CLP组（P〈0．05或P〈0．01）。CLP组肺组织NF-κB、MMP-2、MMP-9的mRNA表达以及BALF中的MMP-2、MMP-9蛋白含量均高于C＋P组（P〈0．05）。结论急性肺损伤时，PTX能够抑制NF-κB活化及MMP-2、MMP-9蛋白的过量表达。抑制炎症反应，减轻肺损伤。Objective To explore the mechanism of how pentoxifylline （PTX）） intervene on nuclear factor- B （NF - κB）, gelatinase （MMP -2, MMP -9） in acute lung injury （ALI）. Methods One hundred and twelve male Kunming mice were randomly divided into four groups： saline control group （NS group）, the pentoxifylline control group （PTX group ）, surgery group （CLP group ）, pentoxifylline treated group （C ＋ P group ）. Made the mode of ALI by cecal ligation and puncture （ CLP）, besidesing the surgical dispose C ＋ P group also administration. The mice were killed at the corresponding time period. Observed histopathologic changes in lung sections and lung NF - κB intensity by immunohistoehemical staining. Expression of NF - κB, MMP - 2, MMP - 9 mRNA was examined by reverse transcription - polymerase chain reaction （ RT - PCR）. Gelatinase （ MMP - 2, MMP - 9 ） concentration in bronchoalveolar lavage fluid （BALF） was determined by enzyme immunoassay （ELISA）. Results Cecal ligation and perforation can cause ALI. CLP mice compared with C ＋ P group was severe pathological manifestations of ALI （ P 〈 0.01 ）. C ＋ P group immunohistochemical staining intensity and area of NF - κB in lung tissue was inferior to the CLP group （ P 〈 0.05 or P 〈 0.01 ）. RT - PCR showed that lung tissue NF - κB, MMP - 2, MMP - 9 mRNA expression were higher of CLP group than that of C ＋ P group （ P 〈 0.05 ）. ELISA results showed that the MMP - 2, MMP - 9 protein levels of CLP group lavage fluid were higher than C ＋ P group （ P 〈 0. 05 or P 〈 0. 01 ）. Conclusion PTX can inhibit NF - κB activation and MMP - 2, MMP - 9 protein over - expression, inhibiting the inflammatory response, reduce lung injury in acute lung injury.

关 键 词：急性肺损伤(ALI) 己酮可可碱 核因子-κB(NF-κB) 明胶酶 支气 管肺泡灌洗液(BALF) 

分 类 号：R576[医药卫生—消化系统]