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左西替利嗪治疗支气管哮喘的疗效及可能机制
引用本文:王华光,张佳丽,王鹤尧.左西替利嗪治疗支气管哮喘的疗效及可能机制[J].中国新药与临床杂志,2007,26(10):751-755.
作者姓名:王华光  张佳丽  王鹤尧
作者单位:首都医科大学附属北京朝阳医院,临床药理基地,北京,100020
摘    要:目的:研究左西替利嗪治疗哮喘的疗效及可能的机制。方法:以卵蛋白致敏法制备大鼠哮喘模型,40只SD大鼠随机分为5组,即正常对照组、哮喘组、地塞米松组、左西替利嗪高剂量组、左西替利嗪低剂量组,各组连续治疗与激发7d后取材。采用ELISA法测定大鼠血清中白细胞介素4(IL-4)、白细胞介素5(IL-5)、肿瘤坏死因子α(TNF-α)的含量;进行支气管肺泡灌洗液(BALF)细胞计数、肺组织嗜酸粒细胞(Eos)计数及病理学观察等。结果:哮喘组IL-4、IL-5、TNF-α较正常对照组均有显著增加(P<0.01);地塞米松组IL-5、TNF-α水平较哮喘组显著降低(P<0.01);左西替利嗪高、低剂量组IL-4、IL-5、TNF-α均较哮喘组减少(P<0.05或P<0.01)。哮喘组BALF中白细胞总数和肺组织Eos计数较正常对照组明显增加(P<0.01);地塞米松组较哮喘组显著减少(P<0.01);左西替利嗪高、低剂量组BALF中白细胞总数与哮喘组相比明显减少(P<0.01),而其肺组织Eos计数与哮喘组相比无显著差异,明显高于地塞米松组(P<0.01)。病理组织学检查可见哮喘组支气管及血管周围有大量Eos浸润等改变,地塞米松组及左西替利嗪高、低剂量组肺组织病理改变均不同程度的轻于哮喘组。结论:左西替利嗪能显著降低哮喘相关细胞因子的水平,因此其可能成为一种新的治疗哮喘的药物。

关 键 词:左西替利嗪  哮喘  细胞因子类
文章编号:1007-7669(2007)10-0751-05
收稿时间:2006-12-22
修稿时间:2007-09-07

Therapeutic efficacy and probable mechanism of levocetirizine in treatment of bronchial asthma
WANG Hua-guang,ZHANG Jia-li,WANG He-yao.Therapeutic efficacy and probable mechanism of levocetirizine in treatment of bronchial asthma[J].Chinese Journal of New Drugs and Clinical Remedies,2007,26(10):751-755.
Authors:WANG Hua-guang  ZHANG Jia-li  WANG He-yao
Institution:Department of Clinical Pharmacology, Beijing Chaoyang Hospital, Capital University of Medical Sciences, BEIJING 100020, China
Abstract:AIM:To investigate the therapeutic efficacy and probable mechanism of levocetirizine in the treatment of bronchial asthma.METHODS:A sensitized asthmatic rat model was obtained by employing ovalbumin challenge.Forty SD rats were randomly divided into five groups:normal group,asthma group, dexamethasone group,levocetirizine high dose group and levocetirizine low dose group.The rats of each group were sacrificed after being treated and challenged for 7 days.The levels of IL-4,IL-5 and TNF-αin the sera were measured by enzyme linked immunosorbent assay(ELISA);the total leucocytes in bronchoalveolar lavage fluid(BALF)and eosinophils(Eos)in lung were counted and pathologic observation was done.RESULTS: The levels of IL-4,IL-5 and TNF-αof asthma group were all significantly higher than those of normal group (P<0.01).The levels of IL-5 and TNF-αof dexamethasone group were significantly lower than those of asthma group(P<0.01).The levels of IL-4,IL-5 and TNF-αof the levocetirizine two groups were all lower than those of asthma group(P<0.05 or P<0.01).The total leucocyte counts in BALF and Los counts in lung of asthma group were markedly increase in comparing with normal group(P<0.01),while those of dexamethasone group were markedly decrease in comparing with the asthma group(P<0.01);the total leucocyte counts in BALF of levoeetirizine two groups were significantly lower than that of asthma group(P<0.01),however,Los counts of the former had no significant differences with the latter but obviously higher than that of dexamethasone group(P<0.01).Histopathological examination showed that the peripheries of bronchi and blood vessels were infiltrated by large amount of eosinophils etc in asthma group,while different degrees of lesser such infiltrations occurred in dexamethasone and levocetirizine high/low dose groups.CONCLUSION:Levocetirizine is able to significantly deerease the asthmatic related cytokines,and probably going to be a new drug for asthma.
Keywords:levocetirizine  asthma  cytokines
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