氟西汀对慢性阻塞性肺疾病模型中炎性因子及糖皮质激素受体水平的影响

Effects of fluoxetine on levels of inflammatory cytokines and glucocorticoid receptors in chronic obstructive pulmonary disease models

目的观察氟西汀治疗对小鼠慢性阻塞性肺疾病模型炎性因子及糖皮质激素受体水平的影响。方法选择雄性C57小鼠为研究对象,随机分为4组,即空白+溶剂组、空白+氟西汀组、熏烟+溶剂组、熏烟+氟西汀组,每组10只。熏烟处理为小鼠连续12周暴露于含有10.0mg焦油和1.0mg尼古丁的香烟烟雾中,建立慢性阻塞性肺疾病模型。空白处理为将小鼠置于充满新鲜空气的箱子中。氟西汀组与溶剂组小鼠分别接受氟西汀和生理盐水灌服,剂量均为5mg/kg。12周后取肺组织做病理切片进行观察,对肺泡灌洗液中炎性因子水平进行分析;同时,分析小鼠海马中糖皮质激素受体(GR)的表达情况。结果小鼠熏烟前的体质量差异无统计学意义(P>0.05);6周后,空白+溶剂组、空白+氟西汀组小鼠体质量显著高于熏烟+溶剂组及熏烟+氟西汀组,差异有统计学意义(P<0.05);12周后,空白+氟西汀组的肺泡灌洗液中白细胞介素(IL)-6和肿瘤坏死因子(TNF)-α水平显著高于空白+溶剂组,差异有统计学意义(P<0.05);熏烟+氟西汀组肺泡灌洗液中IL-6和TNF-α水平明显低于熏烟+溶剂组(P<0.05);与空白+溶剂组相比,熏烟+溶剂组小鼠12周后总GR蛋白水平显著降低(P<0.05);建立慢性阻塞性肺疾病模型后,熏烟+氟西汀组的小鼠体内GR蛋白水平高于熏烟+溶剂组(P<0.05)。结论熏烟导致慢性阻塞性肺疾病小鼠炎性因子水平升高,大脑内的GR蛋白水平持续降低,表达减少。氟西汀能够降低炎性因子的水平,逆转GR蛋白表达的持续降低,有助于慢性阻塞性肺疾病的恢复。

Objective To observe the effect of fluoxetine on the levels of inflammatory cytokines and glucocorticoid receptors in mice with chronic obstructive pulmonary disease(COPD).Methods A total of 40 C57 mice were randomly divided into 4 groups,including blank solvent+saline group,blank solvent+fluoxetine group,smoking+saline group and smoking+fluoxetine group.The rates of smoking group were exposed to cigarette smoke containing 10.0 mg tar and 1.0 mg nicotine for 12 weeks to establish a COPD model.The rates of blank solvent was putted in the boxes full of fresh air.The rates of fluoxetine group and saline group were taken 5 mg/kg intragastric administration of normal saline and fluoxetine.After 12 weeks,the lung tissue was taken for pathological observation,and alveolar lavage fluid was analyzed for inflammatory factors,and the brain was used to analyze the expression of glucocorticoid receptor.Results There was no statistically significant difference in weight of C57 mice before smoking,but after 6 weeks,the weight of blank solvent+saline group and blank solvent+fluoxetine group were significantly higher than that of smoking+saline group and smoking+fluoxetine group(P<0.05).After 12 weeks,interleukin(IL)-6 and tumor necrosis factor(TNF)-αin alveolar lavage fluid of blank solvent+saline group,blank solvent+fluoxetine group,smoking+saline group were significantly higher than that of blank solvent+saline group and smoking+fluoxetine group(P<0.05).Compared with blank solvent+saline group,the level of GR protein of smoking+saline group was significantly decreased(P<0.05).After modeling the COPD,the level of GR protein of smoking+fluoxetine group was significantly higher than that of smoking+saline group.Conclusion The levels of inflammatory cytokines in COPD rats caused by smoking are increased,the levels of GR in the brain are continuously decreased.Fluoxetine could reduce the levels of inflammatory cytokines,reverse the continuous decrease of GR expression,and contribute to the recovery of COPD.