摘要目的 探讨核转录因子-κB抑制蛋白-α(IκBα)和转化生长因子-β1(TGF-β1)在吸烟诱导的大鼠慢性支气管炎中的作用及氨溴索预先给药对慢性支气管炎大鼠IκBα和TGF-β1表达的影响.方法 按随机数字表法将60只雄性Wistar大鼠分为正常组、模型组、低剂量氨溴索组(低剂量组)、高剂量氨溴索组(高剂量组)各15只.采用单纯吸烟的方法建立慢性支气管炎大鼠模型.低剂量组[30 mg/(kg·次)]和高剂量组[75 mg/(kg·次)]经腹腔注射氨溴索,每天吸烟前注射一次至实验结束.模型组于每天吸烟前腹腔内注射与低剂量组等体积生理盐水一次.76 d后将各组大鼠处死,计算各组大鼠支气管肺泡灌洗液(BAFL)中白细胞计数及细胞分类计数;HE染色观察肺组织病理形态学变化;免疫组化法检测IκBα和TGF-β1在大鼠肺组织中的表达.结果 模型组病理形态改变符合慢性支气管炎的特点,高、低剂量组与模型组比较,光镜下慢性支气管炎的改变明显减轻.与正常组比较,模型组BAFL中白细胞总数、中性粒细胞数增高,巨噬细胞数降低,肺组织中IκBα表达明显减弱(t=3.24,3.31,3.29,3.48,P＜0.05),TGF-β1表达明显增强(P＜0.05).高、低剂量组与模型组比较BAFL中白细胞总数、中性粒细胞数降低,巨噬细胞数增高,肺组织中IκBα表达明显增强(t=2.86,2.97,2.92,3.52,2.42,2.88,2.58,3.48,P＜0.05),TGF-β1表达明显减弱(P＜0.05).高剂量组较低剂量组IκBα表达强,TGF-β1表达减弱(t=2.82,3.64,P＜0.05).结论 吸烟诱导的慢性支气管炎大鼠气道炎症可能与IκBα表达下降和TGF-β1表达上升有关;氨溴索可能通过上调IκBα和下调TGF-β1在肺内的表达,发挥抗气道炎症的作用,并且呈现剂量依赖效应.

abstractsObjective To explore the roles of IκBα and TGF-β1 on airway inflammation in rats with chronic bronchitis induced by smoking and study the effects and mechanism of anti-inflammation of pretreatment with ambroxol. Methods Sixty male wistar rats were randomly divided into four groups: Normal dosage group, model group, high dosage group and low dosage group. The rats with chronic bronchitis were established by smoking. For high and low dosage group, rats were pretreated respectively with ambroxol group, rats were pretreated with normal saline through peritoneal injection as much as the low dosage group.After 76 days, the histopathologic changes stained in hemotoxylin and eosin (H. E.) of bronchopulmonary tissues were observed under opticalmicroscope, white cell counts and differential analysis were performed in BALF, the expression of IκBα and TGF-β1 were detected by immunohistochemistry. Results The pathological changes of model group were in consistent with that of chronic bronchitis, but the degrees were significantly reduced in high and low dosage groups. Compared with those in normal group, the white cell count and the neutrophilic granulocyte count of BALF in model group were significantly increased and the macrophagocyte count decreased, and the expression of IκBαwas significantly decreased(t =3.24,3.31,3.29,3.48, P ＜0. 05) and the TGF-β1 significantly increased (P ＜0. 05). Compared with those in the model group, the white cell count and the neutrophilic granulocyte count of BALF in high and low dosage group were significantly decreased and the macrophagocyte count increased, the expression of IκBαwas significantly increased (t =2. 86,2. 97,2. 92,3.52,2.42,2. 88,2. 58,3.48, P ＜0. 05) and the TGF-β1 significantly decreased (P ＜0. 05) . Compared with those in low dosage group, the expression of TGF-β1 was decreased and the expression of IκBαincreased in high dosage group (t =2. 82,3.64, P ＜0. 05). Conclusions Down-regulating the expression of IκBα and up-regulating of TGF-β1 may be involved in the process of airway inflammation in rats with chronic bronchitis induced by smoking. Ambroxol might have better effects on ameliorating airway inflammation by up-regulating the expression of IκBα and down-regulating of TGF-β1.