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目的观察慢性阻塞性肺疾病(COPD)患者中磷脂酰肌醇-3激酶(PI3K)、蛋白激酶B(PKB)与γ-谷氨酰半胱氨酸合成酶(γ-GCS)的表达,研究PI3K、PKB通路和γ-GCS的关系。方法将手术切除的肺癌患者肺组织标本(16例)分为COPD组和对照组,每组8例,检测肺组织中γ-GCS活性,原位杂交检测肺组织中γ-GCS mRNA的表达,免疫组化分析肺组织中PI3K、PKB与γ-GCS的蛋白水平。结果 COPD组中γ-GCS活性明显高于对照组,差异有统计学意义(P<0.01)。原位杂交显示COPD组支气管、肺泡上皮细胞与小动脉平滑肌细胞γ-GCS mRNA广泛表达,与对照组比较差异有统计学意义(P<0.01)。PI3K、PKB与γ-GCS免疫组化在COPD组可见肺泡、支气管壁细胞及小血管平滑肌细胞胞浆中皆有蛋白阳性信号表达,图像定量分析显示COPD组PI3K、PKB与γ-GCS蛋白表达显著高于对照组,差异有统计学意义(P<0.01)。直线相关分析得出PI3K、p-PKB蛋白表达与γ-GCS活性、mRNA及蛋白表达呈正相关。结论COPD患者肺组织γ-GCS蛋白和mRNA表达增高,PI3K、p-PKB蛋白也有相应高表达,提示PI3K、PKB和γ-GCS可能在COPD的发病机制中发挥作用,且可能参与了γ-GCS的信号传导通路。
Objective To observe the expression of phosphatidylinositol 3-kinase (PI3K), protein kinase B (PKB) and γ-glutamylcysteine synthetase (γ-GCS) in patients with chronic obstructive pulmonary disease (COPD) PI3K, PKB pathway and γ-GCS. Methods Sixteen patients with lung cancer undergoing resection were divided into COPD group and control group, with 8 cases in each group. The activity of γ-GCS in lung tissue was detected. The expression of γ-GCS mRNA in lung tissue was detected by in situ hybridization. Immunohistochemistry was used to analyze the protein levels of PI3K, PKB and γ-GCS in lung tissue. Results The activity of γ-GCS in COPD group was significantly higher than that in control group (P <0.01). In situ hybridization showed that the expression of γ-GCS mRNA in bronchus, alveolar epithelial cells and arteriolar smooth muscle cells in COPD group was significantly higher than that in control group (P <0.01). PI3K, PKB and γ-GCS immunohistochemistry in the COPD group showed alveolar, bronchial wall cells and small cell smooth muscle cells in the cytoplasm protein positive signal expression, quantitative analysis showed that COPD group PI3K, PKB and γ-GCS protein expression was significantly Higher than the control group, the difference was statistically significant (P <0.01). Linear correlation analysis showed that PI3K, p-PKB protein expression and γ-GCS activity, mRNA and protein expression was positively correlated. Conclusions The expression of γ-GCS protein and mRNA in lung tissues of COPD patients is increased, while the expressions of PI3K and p-PKB proteins are also high, suggesting that PI3K, PKB and γ-GCS may play a role in the pathogenesis of COPD and may be involved in γ-GCS Of the signal transduction pathway.