Roles Of NF-E2-related Factor2 Signaling Kinases Regulating γ-glutamylcysteine Synthetase In Chronic Obstructive Pulmonary Disease

[Objective] To investigate the expression and relationship of γ- glutamylcysteine synthetase (γ-GCS) and NF-E2-related factor2(Nrf2), P-ERK, P-aPKC_?, P-PKB, G_β in lung of rat and human with chronic obstructive pulmonary disease, to elucidate the possible important role of γ-GCS and Nrf2, P-ERK, P-aPKC_?, P-PKB, G_β in pathogenesis of COPD, and provide theoretical basis and new remedy method for COPD.[Methods] The study was composed of two parts: animal experiment and clinical trial.Part1: Sixteen male Wistar rats were randomly divided into COPD model and control groups. The rat COPD model was established by intratracheal instillation of lipopolysaccharide (LPS200μg/200μL) twice and exposed to cigarette smoke daily. The level of the activity of γ-GCS in lung tissue was measured, the levels of γ-GCS mRNA expression in lung tissue was measured by in site hybridization (ISH) and reverse transcription-polymerase chain reaction (RT-PCR). The protein expression of y-GCS and Nrf2, P- ERK, P-aPKC_?, P-PKB, G_β were observed by immunohistochemistry(IH) and western blot.Part2: Lung tissues from eighteen patients undergoing resection for lung diseasewere drawn,for study, and the expression of Nrf2, P-ERK, P-aPKC_?, P-PKB, G_β<sub><sub>byimmunohistochemical and γ-GCS mRNA by in situ hybridization.[Results]1. PEF, FEV0.3 were decreasing significantly in COPD group compared with control group( all P<0.05), implied airflow obstruction, The pathological findings were consistent with chronic bronchitis and obstructive emphysema.2. The levels of the activity of y-GCS were higher in COPD rat group than that in...