组胺H_1受体拮抗剂对哮喘气道炎症的作用  

Effects of H1receptor antagonists on the airway inflammation of bronchial asthma

作　　者：李寅[1,2] 叶曜芩[1,2] 

机构地区：[1]第二军医大学长征医院呼吸内科 [2]解放军第455医院

出　　处：《第二军医大学学报》1999年第7期409-412,共4页Academic Journal of Second Military Medical University

基　　金：国家自然科学基金

摘　　要：目的：评价Ｈ１受体拮抗剂在哮喘炎症防治中的作用。方法：采用３种治疗方案（生理盐水１ｍｌ／ｄ，酮替芬０．１ｍｇ·ｋｇ－１·ｄ－１，氯雷他定２ｍｇ·ｋｇ－１·ｄ－１），测定３组哮喘豚鼠细胞间粘附分子－１（ＩＣＡＭ－１）、Ｐ－选择素（Ｐ－Ｓ）、白介素８（ＩＬ－８）和嗜酸性粒细胞阳离子蛋白（ＥＣＰ）水平的变化，以及肺功能损害和组织学改变。结果：氯雷他定治疗后，（１）血浆或血清和支气管肺泡灌洗液（ＢＡＬＦ）中ｓＩＣＡＭ－１，ｓＰ－Ｓ，ＥＣＰ和ＢＡＬＦ中ＩＬ－８水平均较对照组下降（Ｐ＜０．０５）；（２）肺组织气道上皮和血管内皮细胞ＩＣＡＭ－１及ＩＬ－８表达明显下调，且氯雷他定效果优于酮替芬（Ｐ＜０．０５）；（３）血白细胞ＩＣＡＭ－１表达明显下调（Ｐ＜０．０５）；（４）动态肺顺应性和潮气量显著提高，气道阻力降低（Ｐ＜０．０５）；（５）气道炎症和嗜酸性粒细胞脱颗粒明显被抑制。结论：新一代的Ｈ１受体拮抗剂氯雷他定具有多方面抗炎作用，本研究可为临床防治哮喘气道炎症提供实验依据。Objective: To investigate the effects of H1receptor (H1R) antagonists on the airway inflammation of asthmatic guinea pigs. Methods: The guinea pigs were divided into 3 groups: loratadine treated group (2 mgkg-1d-1),normal saline group (1 ml/d), and ketotifen treated group (0.1 mgkg-1d-1). The following tests were performed in 3 groups. (a)The ICAM1, PS,IL8 and ECP values both in plasma (or serum )and BALF were measured by ELISA. (b)The expression of ICAM1 and IL8 on the bronchial epithelial cells and pulmonary vascular endothelial cells were measured by immunohistochemistry staining. (c)The expression of ICAM1 on the leukocytes were measured by FCM. (d)The lung functions(Vt, Cdyn, Raw)were tested. (e)The airway tissues were examined by microscope and TEM. Results:T5BZ(a)Apart from the values of IL8 in BALF level of ketotifen group, the values of sICAM1, sPS,IL8 and ECP were reduced by 2 kinds of H1R antagonists(loratadine and ketotifen)both in the plasma(or serum)and BALF of asthmatic animals. (b )The expressions of ICAM1 and IL8 on the brochial epithelial cells and pulmonary vascular endothelial cells in asthmatic animals were downregulated by 2 kinds of H1R antagonists especially loratadine. (c)The expressions of ICAM1 on the leukocytes were downregulated by 2 kinds of H1R antagonists. (d)The lung functions (Vt, Cdyn, Raw) of the asthmatic animals were improved by 2 kinds of H1R antagonists.(e)The infiltration in the bronchial mucosa and the degranulation of eosinophils were reduced by 2 kinds of H1R antagonists. Conclusion: All the results above suggests that H1R antagonists can be used as antiinflammation drugs for the antiinflammative treatment of asthma.

关 键 词：哮喘 豚鼠 H1受体拮抗剂 粘附分子 防治 

分 类 号：R562.250.5[医药卫生—呼吸系统]