摘要
目的探讨西维来司钠对肥胖哮喘大鼠呼吸道炎症的影响。方法96只健康雄性Sprague Dawley大鼠随机分为正常组、肥胖组、肥胖哮喘组和西维来司钠组,每组24只。正常组大鼠给予常规饲料喂养,肥胖组、肥胖哮喘组和西维来司钠组大鼠给予脂肪供能饲料(脂肪供能占60%)喂养,连续喂养16周,建立肥胖大鼠模型,从第9周起,肥胖哮喘组和西维来司钠组大鼠以卵清蛋白(OVA)致敏和激发建立哮喘模型;从第14周起,西维来司钠组大鼠经尾静脉注射西维来司钠(5 mg·kg-1),每日2次,连续3周,肥胖组和肥胖哮喘组大鼠以同样的方式给予等量生理盐水。干预结束后各组大鼠注射不同剂量的乙酰胆碱来检测呼吸道阻力,苏木精-伊红染色观察各组大鼠肺组织病理学变化,并采用Imag-Pro Plus 6.0图像分析软件计算支气管基底膜周径、支气管壁厚度和平滑肌厚度;采用酶联免疫吸附试验检测各组大鼠肺泡灌洗液中白细胞介素(IL)-4、IL-5、IL-8和肿瘤坏死因子-α(TNF-α)水平。结果肥胖组、肥胖哮喘组和西维来司钠组大鼠8周末和处死前体质量均高于正常组(P<0.05),肥胖组、肥胖哮喘组和西维来司钠组大鼠8周末和处死前体质量比较差异均无统计学意义(P>0.05)。注射乙酰胆碱前(给药前)4组大鼠呼吸道阻力比较差异均无统计学意义(P>0.05);正常组和肥胖组大鼠注射各剂量乙酰胆碱后呼吸道阻力比较差异均无统计学意义(P>0.05);肥胖哮喘组和西维来司钠组大鼠注射各剂量乙酰胆碱后呼吸道阻力均高于正常组和肥胖组(P<0.05);西维来司钠组大鼠注射各剂量乙酰胆碱后呼吸道阻力均低于肥胖哮喘组(P<0.05)。正常组和肥胖组大鼠注射0.025 mg·kg-1乙酰胆碱后呼吸道阻力与给药前比较差异无统计学意义(P>0.05);正常组和肥胖组大鼠注射0.050、0.100和0.200 mg·kg^-1乙酰胆碱后呼吸道阻力均高于给药前(P<0.05);肥胖哮喘组和西维来司钠组大鼠注射各剂量乙酰胆碱后呼吸道阻力均高于给药前(P<0.05)。正常组与肥胖组大鼠肺组织结构规则,未见炎性改变;肥胖哮喘组大鼠支气管管壁增厚,黏膜破坏、增生,基底膜增厚,平滑肌细胞增多,肺泡间隔增厚,出现炎症细胞浸润,黏液分泌增多;西维来司钠组大鼠肺泡及支气管周围炎症细胞浸润较肥胖哮喘组减轻,肺泡间隔厚度变小。4组大鼠支气管基底膜周径比较差异无统计学意义(P>0.05)。正常组与肥胖组大鼠支气管壁厚度和平滑肌厚度比较差异无统计学意义(P>0.05);肥胖哮喘组和西维来司钠组大鼠支气管壁厚度和平滑肌厚度大于正常组和肥胖组(P<0.05);西维来司钠组大鼠支气管壁厚度和平滑肌厚度小于肥胖哮喘组(P<0.05)。正常组与肥胖组大鼠肺泡灌洗液中IL-4、IL-5、IL-8和TNF-α水平比较差异均无统计学意义(P>0.05);肥胖哮喘组和西维来司钠组大鼠肺泡灌洗液中IL-4、IL-5、IL-8和TNF-α水平高于正常组和肥胖组(P<0.05);西维来司钠组大鼠肺泡灌洗液中IL-4、IL-5、IL-8和TNF-α水平低于肥胖哮喘组(P<0.05)。结论西维来司钠可减轻肥胖哮喘大鼠呼吸道阻力及支气管重构,其机制可能与抑制呼吸道炎症反应有关。
Objective To investigate the effect of sivelestat sodium on airway inflammation in obese asthma rats.Methods A total of 96 healthy male Sprague Dawley rats were randomly divided into normal group,obese group,obese asthma group and sivelestat group,with 24 rats in each group.The rats in normal group were fed with conventional diet,the rats in the obese group,obese asthma group and sivelestat group were given 60%fat-energy feed for 16 weeks to establish the obese model.From the 9 th week,the rats in the obese asthma group and sivelestat group were sensitized and challenged with ovalbumin(OVA)to establish the asthma model.From the 14 th week,the rats in the sivelestat group were injected with sivelestat via caudal vein at a dose of 5 mg·kg-1,twice a day for 3 weeks;while the rats in the obese group and the obese asthma group were injected with the same amount of physiological saline in the same way.After intervention,the rats in each group were injected with different dose of acetylcholine to detect airway resistance.The pathological changes of lung tissue of rats in each group were observed by hematoxylin-eosin staining,and the circumference of bronchial basement membrane,the thickness of bronchial wall,smooth muscle were calculated by Imag-Pro Plus 6.0 image analysis software.The levels of interleu kin(IL)-4,IL-5,IL-8 and tumor necrosis factor-α(TNF-α)in alveolar lavage fluid of rats in each group were detected by enzymelinked immunosorbent assay.Results The body weights of rats in obese group,obese asthma group and sive lestat group were higher than those in the normal group at the eighth weekend and before execution(P<0.05);there was no statistic difference in the body weight of rats among the obese group,obese asthma group and sirelestat group(P<0.05)There was no significant difference in the airway resistance of rats among the four groups before administration(P>0.05);there was no significant difference in the airway resistance of rats between the normal group and the obese group at different doses of acetylcholine(P>0.05);Compared with the normal group and the obese group,the airway resistance of rats in the obese asthma group and the sivelestat group were increased at each dose of acetylcholine(P<0.05);compared with the obese asthma group,the airway resistance of rats in the sivelestat group were decreased at each dose of acetylcholine(P<0.05).There was no significant difference in airway resistance of rats before administration and after injecting of 0.025 mg·kg-1 acetylcholine in the normal group and the obese group(P>0.05);the airway resistance of rats after injecting of 0.050,0.100 and 0.200 mg·kg-1 acetylcholine was higher than that before administration in the normal group and the obese group(P<0.05);the airway resistance of rats after injecting of each dose of acetylcholine was higher than that before administration in the obese asthma group and the sivelestat sodium group(P<0.05).The lung tissue structure of rats in the normal group and the obese group was regular,and no inflammatory changes were observed.The bronchial wall of rats in obese asthma group was thickened,mucosa was destroyed and proliferated,the basement membrane was thickened,smooth muscle cells were increased,alveolar septum was thickened,inflammatory cells infiltrated and mucus secretion was increased.The infiltration of inflammatory cells in alveoli and peribronchial tissue was less than that in the obese asthma group,and the thickness of alveolar septum was less.There was no significant difference in the perimeter of bronchial basement membrane of rats among the four groups(P>0.05).There was no significant difference in the thickness of bronchial wall and smooth muscle of rats between the normal group and the obese group(P>0.05);the bronchial wall thickness and smooth muscle thickness of rats in the obese asthma group and the sivelestat group were significantly larger than those in the normal group and the obese group(P<0.05);the bronchial wall thickness and smooth muscle thickness of rats in the sivelestat group were significantly smaller than those in the obese asthma group(P<0.05).There was no significant difference in the levels of IL-4,IL-5,IL-8 and TNF-αin the alveolar lavage fluid of rats between the normal group and the obese group(P>0.05);the levels of IL-4,IL-5,IL-8 and TNF-αin the alveolar lavage fluid of rats in the obese asthma group and the sivelestat group were significantly higher than those in the normal group and the obese group(P<0.05);the levels of IL-4,IL-5,IL-8 and TNF-αin the alveolar lavage fluid of rats in the sivelestat group were significantly lower than those in the obese asthma group(P<0.05).Conclusion Sivelestat can alleviate airway resistance and bronchial remodeling in obese asthma rats,and its mechanism might be related to the inhibition of airway inflammation.
作者
杨德彬
郭燕军
胡博
王小稳
YANG De-bin;GUO Yan-jun;HU Bo;WANG Xiao-wen(Department of Respiratory Asthma,the Children′s Hospital Affiliated to Zhengzhou University,Zhengzhou 450018,Henan Province,China;Department of General Internal Medicine,the Children′s Hospital Affiliated to Zhengzhou University,Zhengzhou 450018,Henan Province,China;Department of Emergency,the Children′s Hospital Affiliated to Zhengzhou University,Zhengzhou 450018,Henan Province,China)
出处
《新乡医学院学报》
CAS
2019年第11期1013-1017,共5页
Journal of Xinxiang Medical University
基金
河南省医学科技攻关计划省部共建项目(编号:2018010040)
