
浏览全部资源
扫码关注微信
400014 重庆,重庆医科大学附属儿童医院呼吸科, 儿童发育疾病研究教育部重点实验室,儿童发育重大疾病国家国际科技合作基地,儿科学重庆市重点实验室
[ 符州, E-mail: fu_zhou79@aliyun.com FU Zhou, E-mail: fu_zhou79@aliyun.com
收稿:2017-07-18,
修回:2017-08-18,
纸质出版:2017-11-30
移动端阅览
王亚苹, 邹文静, 蔡霜, 等. 薄荷醇下调肺组织P物质改善哮喘气道炎症及气道高反应性的研究[J]. 第三军医大学学报, 2017,39(22):2151-2156.
Yaping WANG, Wenjing ZOU, Shuang CAI, et al. Menthol improves airway inflammation and hyperresponsiveness in asthmatic mice by reducing substance P in the lungs[J]. Journal of Third Military Medical University, 2017, 39(22): 2151-2156.
王亚苹, 邹文静, 蔡霜, 等. 薄荷醇下调肺组织P物质改善哮喘气道炎症及气道高反应性的研究[J]. 第三军医大学学报, 2017,39(22):2151-2156. DOI: 10.16016/j.1000-5404.201707119.
Yaping WANG, Wenjing ZOU, Shuang CAI, et al. Menthol improves airway inflammation and hyperresponsiveness in asthmatic mice by reducing substance P in the lungs[J]. Journal of Third Military Medical University, 2017, 39(22): 2151-2156. DOI: 10.16016/j.1000-5404.201707119.
目的
2
探讨雾化吸入薄荷醇对哮喘小鼠气道炎症及气道高反应性的作用及其对肺组织P物质(substance P
SP)含量的影响。
方法
2
按随机数字表法将30只6~8周龄BALB/c雌鼠分为对照组、哮喘组及薄荷醇治疗组,哮喘组和薄荷醇治疗组用鸡卵清蛋白(ovalbumin
OVA)致敏激发建立哮喘模型,薄荷醇治疗组于每次雾化激发前给予1.6%薄荷醇溶液5 mL雾化吸入30 min,连续10 d,对照组用PBS替代。于末次雾化24 h内行肺功能检测小鼠气道高反应性;48 h内灌取支气管肺泡灌洗液(bronchoalveolar lavage fluid
BALF)计数细胞总数及细胞分类;肺组织HE染色观察肺部病理改变;ELISA检测血清总免疫球蛋白E(IgE)水平及肺匀浆SP含量;免疫组化染色检测肺组织SP的表达。
结果
2
哮喘组气道高反应性明显高于对照组(
P
<
0.05),而薄荷醇治疗组较哮喘组显著降低(
P
<
0.05);哮喘组BALF细胞总数及嗜酸性粒细胞绝对计数均较对照组明显增加(
P
<
0.01),薄荷醇治疗组较哮喘组显著减少(
P
<
0.01);HE染色显示,哮喘组支气管和血管周围炎症细胞浸润明显,薄荷醇治疗组较哮喘组明显减轻;ELISA结果显示,哮喘组血清总IgE水平及肺匀浆SP含量均较对照组升高(
P
<
0.01),薄荷醇治疗组较哮喘组减轻(
P
<
0.05);免疫组化染色结果显示,哮喘组肺组织SP在气道上皮细胞及血管周围强阳性表达,薄荷醇治疗组中度阳性表达。
结论
2
雾化吸入薄荷醇能减轻哮喘小鼠气道炎症及降低气道高反应性,可能与减少SP含量进而减轻肺部神经源性炎症相关。
Objective
2
To investigate the effect of aerosol inhalation of menthol on airway inflammation
airway hyperresponsiveness and substance P content in the lungs of asthmatic mice.
Methods
2
Thirty female BALB/c mice aged 6-8 weeks were randomly divided into control group
asthma group and menthol treatment group. In the latter 2 groups
the mice were challenged with chicken ovalbumin (OVA) for 10 consecutive days to induce asthma; in menthol treatment group
the mice received inhalation of 5 mL 1.6% menthol solution for 30 min before each challenge. The mice in the control group were treated with PBS only. Within 24 h following the last challenge
the airway hyperresponsiveness (AHR) of the mice was assessed
and the total cell count and eosinophil count in the bronchoalveolar lavage fluid (BALF) were determined within 48 h. HE staining was used to observe the pathological changes in the lungs
and ELISA was used to detect the levels of serum total immunoglobulin E (IgE) and substance P in the lung homogenate; the expression of substance P in the lung tissue was also detected using immunohistochemistry.
Results
2
The asthmatic mice showed a significantly higher level of AHR than the control mice (
P
<
0.05)
and menthol treatment obviously ameliorated AHR in asthmatic mice (
P
<
0.05). The total cell and eosinophil counts in the BALF in asthmatic mice were significantly increased as compared with those in the control group (
P
<
0.001)
and were obviously lowered by menthol treatment (
P
<
0.01). HE staining of the lungs of asthmatic mice revealed obvious inflammatory cell infiltration
which was significantly lessened in menthol-treated mice. Compared with the control group
the asthmatic mice showed significantly elevated serum total IgE level and substance P content in the lung homogenate (
P
<
0.01)
and these elevations were obviously reduced in menthol treatment group (
P
<
0.05). Immunohistochemistry revealed strong expressions of substance P in the airway epithelium and the perivascular tract
but the lung tissues of menthol-treated mice showed only moderate substance P expression.
Conclusion
2
Aerosol inhalation of menthol can reduce airway inflammation and airway hyperresponsiveness in asthmatic mice possibly in relation to its effect of reducing substance P content and neurogenic inflammation in the lungs.
中华医学会儿科学分会呼吸学组.儿童支气管哮喘诊断与防治指南(2016年版)[J].中华儿科杂志, 2016, 54(3): 167-181.
DOI:10.3760/cma.j.issn. 0578-1310.2016.03.003. Pediatrics of Chinese Medical Association Branch of the Breathing Group. Guidelines for the diagnosis and prevention of childhood bronchial asthma (2016 Edition) [J]. Chin J Pediatr, 2016, 54(3): 167-181. DOI: 10.3760/cma.j.issn. 0578-1310.2016.03.003.
CROISANT S. Epidemiology of asthma: prevalence and burden of disease[J]. Adv Exp Med Biol, 2014, 795: 17-29. DOI: 10.1007/978-1-4614-8603-9_2.
FAHY J V. Type 2 inflammation in asthma--present in most, absent in many[J]. Nat Rev Immunol, 2015, 15(1): 57-65. DOI: 10.1038/nri3786.
TAMAOKI J, CHIYOTANI A, SAKAI A, et al . Effect of menthol vapour on airway hyperresponsiveness in patients with mild asthma[J ] . Respir Med, 1995, 89(7): 503-504.
HA M A, SMITH G J, CICHOCKI J A, et al . Menthol attenuates respiratory irritation and elevates blood cotinine in cigarette smoke exposed mice[J ] . PLoS ONE, 2015, 10(2): e0117128. DOI: 10.1371/journal.pone.0117128.
ANDERSEN H H, GAZERANI P, ARENDT-NIELSEN L. High-concentration L-menthol exhibits counter-irritancy to neurogenic inflammation, thermal and mechanical hyperalgesia caused by trans-cinnamaldehyde[J]. J Pain, 2016, 17(8): 919-929. DOI: 10.1016/j.jpain.2016.05.004.
ITO S, KUME H, SHIRAKI A, et al . Inhibition by the cold receptor agonists menthol and icilin of airway smooth muscle contraction[J ] . Pulm Pharmacol Ther, 2008, 21(5): 812-817. DOI: 10.1016/j.pupt.2008.07.001.
LIU B Y, LIN Y J, LEE H F, et al . Menthol suppresses laryngeal C-fiber hypersensitivity to cigarette smoke in a rat model of gastroesophageal reflux disease: the role of TRPM8[J ] . J Appl Physiol, 2015, 118(5): 635-645. DOI: 10.1152/japplphysiol.00717.2014.
SUN J, BHATIA M. Substance P at the neuro-immune crosstalk in the modulation of inflammation, asthma and antimicrobial host defense[J]. Inflamm Allergy Drug Targets, 2014, 13(2): 112-120.
李艳梅, 张慧云, 何韶衡. P物质与肺部疾病[J].江苏医药, 2011, 37(13): 1585-1587.
LI Y M, ZHANG H Y, HE S H. Substance P and lung diseases[J]. Jiangsu Med, 2011, 37(13): 1585-1587.
NIU C, LIU N, LIU J, et al . Vitamin A maintains the airway epithelium in a murine model of asthma by suppressing glucocorticoid-induced leucine zipper[J ] . Clin Exp Allergy, 2016, 46(6): 848-860. DOI: 10.1111/cea.12646.
TRIANTAPHYLLOPOULOS K, HUSSAIN F, PINART M, et al . A model of chronic inflammation and pulmonary emphysema after multiple ozone exposures in mice [J ] . Am J Physiol Lung Cell Mol Physiol, 2011, 300(5): L691-700.DOI: 10.11 52/ajplung.00252.2010.
ZHAO L, ZHUANG J, ZANG N, et al . Prenatal nicotinic exposure upregulates pulmonary C-fiber NK1R expression to prolong pulmonary C-fiber-mediated apneic response[J ] . Toxicol Appl Pharmacol, 2016, 290: 107-115. DOI: 10.1016/j.taap.2015.10.023.
沈梅芳, 李小萌, 单琪媛.薄荷化学成分与药理作用研究新进展[J].中华中医药学刊, 2012, 30(7): 1484-1487. DOI: 10.13193/j.archtcm.2012.07.46.shenmf.051.
SHEN M F, LI X M, SHAN Q Y. Research progress of chemical compositions and pharmacological actions of mentha canadensis[J]. Chin Arch Trad Chin Med, 2012, 30(7): 1484-1487.DOI:10.13193/j.archtcm.2012.07.46.shenmf.051.
OZ M, NEBRISI E G E, YANG K H S, et al . Cellular and molecular targets of menthol actions[J ] . Front Pharmacol, 2017, 8: 472. DOI: 10.3389/fphar.2017.00472.
PALOMARESÓ, SÁNCHEZ-RAMÓN S, DÁVILA I, et al . dIvergEnt: How IgE axis contributes to the continuum of allergic asthma and anti-IgE therapies[J ] . Int J Mol Sci, 2017, 18(6): 1328. DOI: 10.3390/ijms18061328.
FROIDURE A, MOUTHUY J, DURHAM S R, et al . As thma phenotypes and IgE responses[J ] . Eur Respir J, 2016, 47(1): 304-319. DOI: 10.1183/13993003.01824-2014.
ZAIA M G, TD C, FEITOSA K A, et al . Anti-inflammatory properties of menthol and menthone in Schistosoma mansoni infection[J ] . Front Pharmacol, 2016, 7: 170. DOI: 10.3389/fphar.2016.00170..
RAMALHO R, ALMEIDA J, BELTR O M, et al . Substance P antagonist improves both obesity and asthma in a mouse model [J ] . Allergy, 2013, 68(1): 48-54. DOI: 10.1111/all.12052.
DEVOS F C, BOONEN B, ALPIZAR Y A, et al . Neuro-immune interactions in chemical-induced airway hyperreactivity[J ] . Eur Respir J, 2016, 48(2): 380-392. DOI: 10.1183/13993003.01778-2015.
MAHER S A, BIRRELL M A, BONVINI S J, et al . P6 menthol has beneficial effects in the airways through a Trpm8-independent mechanism[J ] . Thorax, 2014, 69(Suppl 2): A79-A80.
LEEL Y. Respiratory sensations evoked by activation of bronchopulmonary C-fibers[J]. Respir Physiol Neurobiol, 2009, 167(1): 26-35. DOI: 10.1016/j.resp.2008.05.006.
0
浏览量
0
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621