糖尿病大鼠肺组织中核转录因子-κB及其抑制因子信号通路的表达变化

Changes of expression of signaling pathway of NF-κB/IκB in rat lung tissue with diabetes

目的 探讨核转录因子-κB（NF-κB）信号通路激活对糖尿病肺损伤的影响.方法 通过高糖、高脂饮食加腹腔注射小剂量链尿佐菌素（STZ）的方法,建立2型糖尿病大鼠模型,采用光镜动态观察12、24周时,对照组（20只）、糖尿病组（30只）大鼠肺组织的形态学改变情况,用Masson三色染色观察肺组织胶原沉积情况,应用免疫组织化学方法检测2组肺组织NF-κB p65、IκBα、蛋白激酶C的变化情况.结果 光镜下糖尿病大鼠肺组织结构紊乱,肺泡间隔增厚,周围细胞外基质增多,局部纤维化,随病情进展,表达愈加明显.12、24周糖尿病大鼠肺组织NF-κB p65的吸光度值为0.20±0.0l、0.35±0.06,高于同期对照组的0.12±0.02、0.17±0.03,差异有统计学意义（P均＜0.01）,12、24周糖尿病肺组织IκB的吸光度为0.29±0.02、0.36±0.03,分别高于同期对照组的0.08±0.02、0.22±0.08,差异有统计学意义（P均＜0.01）.结论 NF-κB及其IκB信号通路的激活参与糖尿病肺组织病变的发生发展,可能是肺损伤的机制之一.

Objective To investigate the effect of activation of NF-κB signaling pathway on pathogenesis of lung in diabetes mellitus（DM） rat. Methods The experimental type 2 diabetic rats were built by injecting streptozotocin （STZ） and feeding with high fat and glucose food. At the 12nd and 24th week, we observed the alteration of morphology in the lung of rats in the control group（20 rats） ,the DM group（30 rats）using spectroscopic analysis. The collagen accumulation of lung was observed by masson trihrome staining, and alteration of NF-κB P65, IκBα, and PKC in lung was observed by immunohistochemistry. Results The tissue structure of lung in the DM rats distributed deranged in the light microscope, alveolar wall were thicken, extracellular matrixes increased and pulmonary fibrosis appeared. With the development of pathogenic condition, the expression increased obviously. The staining optical density value of NF-κB P65 in tissue of lung in the 12 w and 24 w DM group were 0. 20 ± 0. 01 and 0. 35 ± 0. 06 respectively, which was significantly higher than those of the control group at the corresponding time point （ 0. 12 ± 0. 02 and 0. 17 ± 0. 03, respectively, Ps 〈 0. 0l ）. The staining optical density value of IκB in tissue of lung in the 12 w and 24 w DM group were 0. 29 ±0. 02 and 0. 36 ± 0. 03, respectively, which were significantly higher than those of the control at the corresponding time point （0. 08 ± 0. 02 and 0. 22 ± 0. 08, respectively, Ps 〈 0. 01 ）. Conclusion The signaling pathway of NF-κB/IκB participate in the occurrence and development in the pathogenesis of lung in DM, and may be one of the mechanisms of lung injury.