摘要
目的通过观察巨噬细胞炎症蛋白-1α(MIP-1α)和核因子-κB(NF-κB)在机械通气大鼠肺组织中的表达,探讨MIP-1α及NF-κB在呼吸机所致肺损伤(VILI)发生中的作用。方法 32只雄性健康Wistar大鼠随机分为对照组、小潮气量组、常规潮气量组和大潮气量组。分别采用原位分子杂交技术和免疫组织化学染色方法检测各组大鼠肺组织MIP-1α mRNA及NF-κB p65蛋白表达水平,测定其支气管肺泡灌洗液(BALF)中白细胞及中性粒细胞计数。结果大潮气量组和常规潮气量组大鼠BALF中白细胞和中性粒细胞计数,以及细支气管上皮MIP-1α mRNA和NF-κB p65蛋白阳性表达细胞百分比均明显高于小潮气量组和对照组(P<0.01)。对照组与小潮气量组比较差异无统计学意义(P>0.05)。相关分析结果表明,各组大鼠细支气管上皮MIP-1α mRNA阳性表达细胞百分比与BALF中性粒细胞计数和NF-κB p65蛋白阳性表达细胞百分比之间均呈正相关(r=0.546,r=0.482,均P<0.05)。结论在VILI发生过程中,MIP-1α是导致中性粒细胞在肺内募集、活化的重要细胞因子;肺组织细胞表达MIP-1α在一定程度上可能受NF-κB的调控;机械刺激→NF-κB→MIP-1α信号通路可能是VILI发生过程中细胞内信号传导途径之一。
Objective To determine the pulmonary macrophage inflammatory protein-let （MIP-1α
and nuclear faetor-κB （NF-κB） expression and their roles in ventilator-induced lung injury （VILI） in rats treated with mechanical ventilation. Methods Thirty-two health male Wistar rats were randomly assigned to control, low tidal volume, con-ventional tidal volume and high tidal volume group, respectively. The expression of MIP-1α mRNA and NF-κB p65 protein in lung tissues was detected by in situ hybridization and immunohistochemistry for measurement of white blood cell （WBC） and neutrophil count. Results Compared with low tidal volume and control group, significantly higher WBC and neutrophil count in bronchoalveolar lavage fluid （BALI7） and increased positivity of MIP-1α mRNA and NF-κB p65 protein expression in bronchiole epithelia was found in the high-and conventional tidal volume group （both P〈0.01）. The difference between low tidal volume group and control group was unremarkable （P〉0.05）. There was a positive correlation between the positivity of MIP-1α mRNA expression in the bronehiole epithelia and BALF neu- trophil count （r=0.546, P〈0.05） and the positivity of NF-κB p65 protein expression in bronchiole epithelia in all groups （r=0.482, P〈0.05）. Conclusion MIP-1α may play an important role in pulmonary neutrophil recruitment and activation in the pathogenesis of VILI. The expression of MIP-1α in the lung tissues may be, to a certain extent, gov-erned by NF-κB. The signaling pathway of mechanical stimulation-NF-κB-MIP-1α may be a critical link of cellular signaling in the development of VILI.
出处
《中国药物与临床》
CAS
2013年第7期865-867,共3页
Chinese Remedies & Clinics
基金
山西省科技攻关项目(2007032016-1)
太原市科技资助项目(0801041)
