间歇低氧-肺气肿大鼠的炎症及免疫反应特点研究

摘要:目的 建立间歇低氧(IH)-肺气肿大鼠模型, 探讨其引起炎症和免疫反应的特点。方法 60 只 Wistar 大鼠随机分成对照组、 肺气肿组、 IH 组和重叠组(肺气肿合并 IH 组)。每组 15 只。造模成功后使用流式细胞仪测定各组外周血中性粒细胞 （PMN）、 CD3+ CD8+ T 细胞、 CD3+ CD4+ T 细胞凋亡率水平。酶联免疫吸附试验 （ELISA） 法测定血浆中肿瘤坏死因子(TNF)-α、 白细胞介素 （IL） -6 水平。取大鼠肺泡灌洗液(BALF), 在光镜下计算巨噬细胞、 外周血 PMN 和淋巴细胞比例。采集肺、 肝脏、 胰腺组织和右颈动脉并进行病理评分。结果 重叠组中 PMN、 CD3+ CD8+ T 细胞凋亡率与其他 3 组相比较低, CD3+ CD4+ T 细胞凋亡率、 TNF-α、 IL-6 表达水平最高 （均 P < 0.05）。BALF 中, 肺气肿组巨噬细胞和 PMN 百分比高于其余 3 组 （均 P < 0.05）。重叠组中肺、 肝脏、 胰腺、 右颈动脉内中膜厚度的病理评分高于其他 3组 （均 P < 0.05）。结论 肺气肿合并IH 可产生更严重的系统性多器官炎症和免疫反应。

Inflammatory and immune responses in a rat model of intermittent hypoxia-emphysema

Abstract：Objective To develop an "overlap syndrome (OS)" rat model by intermittent hypoxia (IH) exposure on the base of pre- existing emphysema, and to explore its characters of severe systemic inflammation and immune responses. Methods Sixty Wistar rats were put into four groups: control group, IH group, emphysema group and overlap (emphysema+ IH) group. The peripheral blood samples were collected for detecting apoptosis of CD3+ CD4+ , CD3+ CD8+ T lymphocytes and neutrophils (PMN). Tumor necrosis factor (TNF)-α and interleukin (IL)-6 were evaluated by ELISA. The bronchoalveolar la⁃ vage fluid (BALF) was taken to calculate the ratio of macrophages, neutrophils and lymphocytes under light microscope. Tis⁃ sue blocks of lung, liver, pancreas, and right carotid artery were taken for pathologic scoring. Results The apoptotic rates of PMN and CD3 + CD8 + T cells were significantly lower in overlap group than those of other three groups (P < 0.05). Pro-in⁃ flammatory factor IL-6, TNF-α and peripheral blood CD3 + CD4 + T cell apoptosis were the highest in overlap group com⁃ pared to those of other three groups (P < 0.05). The ratio of PMN and macrophages in BALF were significantly higher in em⁃ physema group than those of other three groups (P < 0.05) and the pathology scores of lung, liver, pancreas, the ratio of carot⁃ id artery intima-media thickness of whole thickness of vascular were significantly higher in overlap group than those of other three groups (P < 0.05).Conclusion In rat model of intermittent hypoxia- emphysema there are more serious systemic multi-organ inflammation and immune responses.