[1]杨德彬,郭燕军,胡　博,等.西维来司钠对肥胖哮喘大鼠呼吸道炎症的影响[J].新乡医学院学报,2019,36(11):1013-1017.[doi:10.7683/xxyxyxb.2019.11.003]
　YANG De-bin,GUO Yan-jun,HU Bo,et al.Effect of sivelestat sodium on airway inflammation in obese asthma rats[J].Journal of Xinxiang Medical University,2019,36(11):1013-1017.[doi:10.7683/xxyxyxb.2019.11.003]
点击复制

西维来司钠对肥胖哮喘大鼠呼吸道炎症的影响
分享到：

《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
36
期数:
2019年11
页码:
1013-1017
栏目:
基础研究
出版日期:
2019-11-05

文章信息/Info

Title:
Effect of sivelestat sodium on airway inflammation in obese asthma rats
作者:
杨德彬1; 郭燕军2; 胡　博3; 王小稳3
（1.郑州大学附属儿童医院呼吸哮喘科，河南　郑州　450018；2.郑州大学附属儿童医院普内科，河南　郑州　450018；3.郑州大学附属儿童医院急诊科，河南　郑州　450018）
Author(s):
YANG De-bin1; GUO Yan-jun2; HU Bo3; WANG Xiao-wen3
(1.Department of Respiratory Asthma，the Children′s Hospital Affiliated to Zhengzhou University，Zhengzhou 450018，Henan Province,China;2.Department of General Internal Medicine，the Children′s Hospital Affiliated to Zhengzhou University，Zhengzhou 450018，Henan Province,China；3.Department of Emergency，the Children′s Hospital Affiliated to Zhengzhou University，Zhengzhou 450018，Henan Province,China)
关键词:
西维来司钠; 肥胖; 哮喘; 气道炎症; 大鼠
Keywords:
sivelestat; obesity; asthma; airway inflammation; rat
分类号:
R562.25
DOI:
10.7683/xxyxyxb.2019.11.003
文献标志码:
A
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。
Abstract:
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 9th 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 14th 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 interleukin(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-1acetylcholine 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-1acetylcholine 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-α in 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-α in 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).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.

参考文献/References:

［1］　顾景范.《中国居民营养与慢性病状况报告（2015）》解读［J］.营养学报，2016，38(6):525-529.
［2］　郑嫆颖，张维溪.肥胖和哮喘相关气道高反应性的研究进展［J］.中华医学杂志，2018，98(32):2609-2611.
［3］　闫冰，庞随军.儿童肥胖的危害研究进展［J］.新乡医学院学报，2018，35（9）：840-843.
［4］　MARKO M，PAWLICZAK R.Obesity and asthma: risk，control and treatment［J］. Postepy Dermatol Alergol, 2018，35(6):563-571.
［5］　SZCZEPANKIEWICZ D，SKRZYPSKI M，PRUSZY N＇SKA-OSZMA　 LEK E，et al.Interleukin 4 affects lipid metabolism and the expression of pro-inflammatory factors in mature rat adipocytes［J］.Immunobiology，2018，223(11):677-683.
［6］　金祝华，匡永勤，李天泉，等.中性粒细胞弹性蛋白酶抑制剂对脑出血患者术后氧化应激、炎性介质的影响［J］.临床神经外科杂志，2018，15(3):213-217.
［7］　王后红，李国刚，李超，等.西维来司钠对急性坏死性胰腺炎肺损伤保护作用及其机制研究［J］.中华急诊医学杂志，2016，25(1):63-66.
［8］　曾泽宇，孔璐丹，张维溪，等.雷公藤红素对肥胖型哮喘气道高反应的影响［J］.医学研究杂志，2017，46(4):28-31.
［9］　LIM M S，LEE C H，SIM S，et al.Physical activity，sedentary habits，sleep，and obesity are associated with asthma，allergic rhinitis，and atopic dermatitis in Korean adolescents［J］. Yonsei Med J，2017，58(5):1040-1046.
［10］　韦润红，陈疏敏，陈艳丽.肥胖对哮喘患儿吸入布地奈德疗效、肺功能及血清因子的影响［J］.中国现代医学杂志，2018，28(30):67-72.
［11］　陈治宇，邓俊，梁宇佳，等.吡格列酮对肥胖哮喘大鼠气道重塑的影响及与瘦素的关系［J］.重庆医学，2018，47(36):4570-4574，4579.
［12］　LIANG L，HUR J，KANG J Y，et al.Effect of the anti-IL-17 antibody on allergic inflammation in an obesity-related asthma model［J］.Korean J Intern Med，2018，33(6):1210-1223.
［13］　苏毅，杜雪梅，郝月琴，等.吸入布地奈德对肥胖哮喘小鼠气道炎症及瘦素水平的影响［J］.中华实用诊断与治疗杂志，2015，29(11):1091-1094.
［14］　WEN X，XU X，SUN W，et al.G-protein-coupled formyl peptide receptors play a dual role in neutrophil chemotaxis and bacterial phagocytosis［J］.Mol Biol Cell，2019，30(3):346-356.
［15］　李和林，吕琪，肖培欣，等.西维来司钠组对烟雾吸入性肺损伤大鼠早期炎症反应的影响［J］.天津医药，2017，45(9):916-919.
［16］　HILL L A，VASSILIADI D A，DIMOPOULOU I，et al.Neutrophil elastase-cleaved corticosteroid-binding globulin is absent in human plasma［J］.J Endocrinol，2019，240(1):27-39.

相似文献/References:

[1]宋晓敏　杨　冰　杜　玮　郭长磊　李根旺　邬玉芳　郭丽萍.豆番粉与玉米粉对人体血糖胰岛素胰升血糖素的影响[J].新乡医学院学报,1998,15(03):234.
[2]杜玮,秦海梅,徐青.2型糖尿病肥胖患者66例代谢紊乱临床分析[J].新乡医学院学报,2005,22(04):000.
[3]王润之,黄艳群.LPIN1基因的研究进展[J].新乡医学院学报,2010,27(04):413.
[4]张　瑶１,２,叶建平２. 肥胖引发的炎症是保护反应[J].新乡医学院学报,2015,32(08):695.
[5]马斐斐,曹丁丁,李　伟,等.趋化因子CXCL1在肥胖小鼠脂肪组织中的表达及意义[J].新乡医学院学报,2016,33(10):849.[doi:10.7683/xxyxyxb.2016.10.003]
　MA Fei-fei,CAO Ding-ding,LI Wei,et al.Expression and significance of chemokine CXCL1 in the adipose tissue of mice with obesity[J].Journal of Xinxiang Medical University,2016,33(11):849.[doi:10.7683/xxyxyxb.2016.10.003]
[6]张　艳,杨勇锋,张红星,等.精神分裂症患者性别差异研究[J].新乡医学院学报,2018,35(9):784.[doi:10.7683/xxyxyxb.2018.09.008]
　ZHANG Yan,YANG Yong-feng,ZHANG Hong-xing,et al.Gender differences in patients with schizophrenia[J].Journal of Xinxiang Medical University,2018,35(11):784.[doi:10.7683/xxyxyxb.2018.09.008]
[7]姜晓旭,李明哲,赵九洲,等.巨噬细胞在肥胖进程中的作用研究进展[J].新乡医学院学报,2019,36(7):694.[doi:10.7683/xxyxyxb.2019.07.024]
[8]聂　婵,于慧婷,石修权.肥胖对烧伤患者治疗效果及预后的影响研究进展[J].新乡医学院学报,2018,35(11):1033.[doi:10.7683/xxyxyxb.2018.11.022]
　N/A.N/A[J].Journal of Xinxiang Medical University,2018,35(11):1033.[doi:10.7683/xxyxyxb.2018.11.022]
[9]温西苹,李元霞.儿童哮喘相关危险因素研究进展[J].新乡医学院学报,2019,36(11):1092.[doi:10.7683/xxyxyxb.2019.11.021]
[10]王文茜,开　悦,刘　虎,等.高脂饮食对小鼠不同组织中成纤维细胞生长因子21及其受体表达的影响[J].新乡医学院学报,2020,37(4):318.[doi:10.7683/xxyxyxb.2020.04.004]
　WANG Wenqian,KAI Yue,LIU Hu,et al.Effect of high fat diet on the expression of fibroblast growth factor 21 and its receptors in different tissues of mice[J].Journal of Xinxiang Medical University,2020,37(11):318.[doi:10.7683/xxyxyxb.2020.04.004]

更新日期/Last Update: 2019-11-05