布地奈德对哮喘大鼠肺泡Ⅱ型上皮细胞的影响

Effect of Budesonide on alveolar type Ⅱ epithelial cells in asthmatic rats

目的观察吸入糖皮质激素对哮喘大鼠肺泡Ⅱ型上皮细胞(AT-Ⅱ)的影响。方法42只Wistar大鼠随机分为正常对照组(C组)、哮喘组(A组)和布地奈德组(BUD组),每组14只。用卵白蛋白(OVA)制备哮喘大鼠模型并观察肺组织病理和超微结构变化及BUD干预后的影响;测定各组大鼠支气管肺泡灌洗液(BALF)中肿瘤坏死因子-α(TNF-α)浓度和AT-Ⅱ细胞的损伤情况;将凋亡和坏死细胞之和占检测细胞总数的百分比(总损伤率)与BALF中TNF-α浓度进行相关分析。结果A组大鼠存在AT-Ⅱ细胞变性、坏死、崩解、脱落、板层体空泡化及嗜锇性物质脱落等超微结构变化。A组BALF中的TNF-α浓度(93.23±19.84)pg.mL-1分别显著高于C组的(26.97±5.85)pg.mL-1和BUD组的(38.24±6.41)pg.mL-1;A组AT-Ⅱ细胞的凋亡率和坏死率分别为(11.55±2.82)%和(10.69±3.99)%,均高于C组的(2.81±2.22)%和(1.84±0.95)%以及BUD组的(2.05±1.53)%和(5.79±2.47)%;BALF中TNF-α与AT-Ⅱ细胞总损伤率呈显著正相关(r=0.864,P<0.01)。结论哮喘大鼠BALF中TNF-α水平增高,AT-Ⅱ细胞损伤现象明显。通过抑制TNF-α的生成和/或释放可能是吸入BUD对AT-Ⅱ细胞有保护作用的重要机制。

OBJECTIVE To study the effect of inhaled glucocorticosteroid on alveolar type Ⅱ epithelial cells （AT-Ⅱ ） in asthmatic rats. METHODS In the experiment, the Wistar rat model of asthma was established by the ovalbumin （OVA） challenge methods and the histopathology and ultrastructure changes of lung tissues were observed.The concentrations of tumor necrosis factor-alpha（TNF-α） in BALF were measured and the injury status of AT- Ⅱ cells was detected. Correlation analysis between the total injury （including apoptosis and necrosis） rates of AT- Ⅱ cells and the concentrations of TNF-α in BALF was performed. RESULTS AT- Ⅱ cells showed degeneration, necrosis, shedding, lamellar bodies vacuolization and destruction in asthma group. Respectively, the concentrations of TNF-α in BALF of control group （（26.97 ± 5.85）pg·mL^-1 and budesonide-treated group [（38.24 ±6.41） pg·mL^-1 were lower than that of asthma group [（93.23± 19.84） pg·mL^-1） .The apoptosis and necrosis rates of AT- Ⅱ cells of asthma group [（11.55 ± 2.82） % and （10.69 ± 3.99） %] were higher than that of control group [（2.81 ±2.22）% and （1.84±0.95） %] and budesonide-treated group [（2.05 ± 1.53）% and （5.79 ± 2.47） % ] respectively. There was a significantly positive correlation between the concentrations of TNF-α in BALF and the total injury rates of AT-Ⅱ cells[（r=0.864, P〈0.01）] .CONCLUSION The concentrations of TNF-α in BALF is increased and the injury of AT- Ⅱ cells is significant in asthmatic rats. The cytoprotection of budesonide to AT- Ⅱ cells is partly related to inhibit the production and/or release of TNF-α.