慢性阻塞性肺疾病大鼠NRF2和γ-谷氨酰半胱氨酸合成酶表达的改变  

ROLES OF NRF2 REGULATING γ-GLUTAMYLCYSTEINE SYNTHETASE IN LUNG OF RATS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE

作　　者：陈林[1] 戴爱国 胡瑞成 

机构地区：[1]湖南省老年医院,湖南省老年医学研究所呼吸疾病研究室

出　　处：《中国应用生理学杂志》2008年第3期339-342,I0002,共5页Chinese Journal of Applied Physiology

基　　金：湖南省科技计划项目(01JZY2017;05JT1023);湖南省医药卫生科研课题(B2005125)

摘　　要：目的:通过观察慢性阻塞性肺疾病(COPD)大鼠肺内红系衍生的核因子2相关因子2(NRF2)和γ-谷氨酰半胱氨酸合成酶(γ-GCS)的表达,探索NRF2调控γ-GCS在COPD发病中可能的参与机制。方法:雄性Wistar大鼠16只,随机分COPD模型组和对照组。检测γ-GCS活性,γ-GCS的基因表达和NRF2的蛋白质表达。结果:γ-GCS活性在COPD组中明显高于对照组。γ-GCSmRNA广泛高表达于COPD组支气管平滑肌细胞,而对照组相应部位呈弱表达。对照组肺匀浆中有一定量γ-GCSmRNA表达,但相对于COPD组仍较低。NRF2、γ-GCS在COPD组支气管上皮细胞胞浆中高表达,而对照组相应部位中呈弱表达。COPD组γ-GCS和NRF2蛋白表达皆有明显上调。NRF2蛋白表达与γ-GCS蛋白、mRNA表达呈正相关关系。结论:氧化应激可能通过使NRF2转录活性增加的方式上调NRF2,进而上调γ-GCS的表达,在COPD的发病中起重要作用。Aim： To investigate the expression and relationship of γ-glutamylcysteine synthetase （γ-GCS） and NF-E2-related factor2 （NRR2） in lung of rat with chronic obstructive pulmonary disease（COPD）in order to elucidate the possible important role of γ-GCS and NRF2 in pathogenesis of COPD. Methods： The rat COPD model was established by intratracheal instillation of lipopolysaccharide twice and exposed to cigarette smoke daily. The γ-GCS activity was measured, the expression of γ-GCS mRNA in lung was exa mined by in situ hybridization （ISH） and reverse transcription-polymerase chain reaction （RT-PCR）, the protein expressions of NRF2 ,γ-GCS in lung were detected by immunohistochemical（IH） and Western blot respectively. Results： The γ-GCS activity was higher in COPD group than that in control group. The expressions of γ-GCS mRNA in COPD group was stronger than those in control group. ISH showed that the γ-GCS mRNA was expressed in alveolar epithelium and bronchial smooth muscle cell in COPD. The protein expressions of NRF2, γ-GCS were significantly higher than the control group. IH showed that NRF2 ,γ-GCS proteins were ex pressed in alveolar and bronchial epithelium in the COPD group. There was a positive correlation between NRF2 and γ-GCA and γ-GCS mRNA. Conclusion： NRF2 may play an important role in the mechanism of COPD oxidative stress vis up-regulation of γ-GCS.

关 键 词：阻塞性肺疾病 Γ-谷氨酰半胱氨酸合成酶 基因调控 

分 类 号：Q74[生物学—分子生物学] R45[医药卫生—治疗学]