乙酰辅酶A羧化酶激动剂柠檬酸钠对慢性哮喘小鼠气道炎症和气道重塑的作用

Effect of acetyl-CoA carboxylase activator sodium citrate on airway inflammation and airway remodeling in mice with chronic asthma

目的:观察乙酰辅酶A羧化酶(ACC)激动剂柠檬酸钠(SCT)对慢性哮喘小鼠气道炎症和气道重塑的作用。方法:18只雌性BALB/c小鼠随机分成3组,即对照组(PBS组)、哮喘组(OVA组)、乙酰辅酶A羧化酶激动剂组(SCT组),每组6只。哮喘组和SCT组给予卵清蛋白(OVA)致敏和激发,对照组对应给予等体积磷酸盐缓冲液(PBS)处理。其中SCT组于每次激发前30 min腹腔注射溶于PBS的SCT。最后一次激发24 h后,取小鼠肺组织用于检测组织病理学变化。HE染色观察炎症细胞浸润,以评估小鼠气道炎症。PAS染色观察杯状细胞增生,Masson染色观察上皮下胶原沉积,α-SMA免疫组织化学染色观察平滑肌细胞增生与肥大。结果:HE染色表明,OVA组和SCT组气道炎症细胞浸润评分均显著高于PBS组,且SCT组显著高于OVA组(P<0.01)。PAS染色显示,OVA组和SCT组气道杯状细胞增生均高于PBS组,且SCT组高于OVA组(P<0.05)。Masson染色发现,OVA组和SCT组气道上皮下胶原沉积高于PBS组,且SCT组高于OVA组(P<0.01)。α-SMA免疫组织化学染色显示,OVA组和SCT组气道平滑肌增生均高于PBS组,且SCT组高于OVA组(P<0.05)。结论:SCT干预后,慢性哮喘小鼠气道炎症及气道重塑指标均加重,提示ACC活化可能加重哮喘气道炎症和气道重塑。

Objective: To investigate the effect of acetyl-Co A carboxylase activator sodium citrate(SCT) on airway inflammation and airway remodeling in mice model of chronic asthma.Methods: Eighteen female BALB/c mice were randomly divided into three groups(six mice in each group), namely a control group(PBS group), an asthma group(OVA group), and an acetyl-Co A carboxylase activator sodium citrate group(SCT group). The asthma group and the SCT group were sensitized and challenged with ovalbumin(OVA) while the control group was challenged with equal volume phosphate buffer saline(PBS). The SCT group was intraperitoneally administrated with SCT dissolved in PBS 30 min before each challenge. The lungs were collected 24 h after the last challenge. Airway inflammation was evaluated with HE staining to observe the infiltration of inflammatory cells. Periodic acid-Schiff(PAS) staining was performed to evaluate goblet cell hyperplasia, and Masson-trichrome staining was used to evaluate the deposition of collagen matrix. In addition, immunohistochemical analysis of the α-smooth muscle actin(α-SMA) was applied to examine airway smooth muscle cell hyperplasia and hypertrophy.Results: The HE staining revealed that the inflammatory cell infiltration in OVA group and SCT group was significantly increased as compared with that in PBS group, and it was higher in SCT group than in OVA group(P<0. 01). The PAS staining proved that the goblet cell hyperplasia was significantly increased in OVA group and SCT group as compared with the PBS group, and it was also higher in SCT group than in OVA group(P<0. 05). The Masson staining showed that the collagen deposition in OVA group and SCT group increased significantly as compared with that in PBS group, and collagen levels in SCT group was also higher than in OVA group(P<0. 01). The α-SMA immunohistochemical analysis demonstrated that the expression of α-SMA in OVA group and SCT group increased significantly as compared with that in PBS group, and there was also a significant different between SCT groupand OVA group(P<0. 05).Conclusion: ACC activation with SCT increased the indicators of airway inflammation and airway remodeling in chronic asthma mice, suggesting that ACC activation may aggravate the airway inflammation and airway remodeling in asthma.