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组胺在哮喘豚鼠气道重塑中的作用

王向红, 刘声远, 陈宝生, 余上斌, 叶仕乔, 陈琪玲

华中科技大学同济医学院病理生理系.湖北，武汉 430030；河南科技大学法医系.河南，洛阳 471003

摘要

该研究旨在探讨组胺在哮喘豚鼠气道重塑中的作用。将 50只健康雄性豚鼠随机分为5组。正常对照组: 雾化吸入蒸馏水8周；哮喘模型组: 致敏后雾化吸入卵白蛋白(ovalbumin, OVA) 8周；哮喘模型延续组: 致敏后雾化吸入OVA 14周；组胺组: 致敏后雾化吸入OVA 14周，最后6周同时加用组胺；组胺受体拮抗剂组: 致敏后雾化吸入OVA 14周，最后6周同时加用组胺受体拮抗剂。检测血清组胺、 Na~(+)、Cl~(-)浓度、动脉血氧分压(PaO_(2))、动脉血二氧化碳分压(PaCO_(2))、pH、实际碳酸氢盐(actual bicarbonate, AB)、标准碳酸氢盐(standard bicarbonate, SB)以及气道壁粘膜层、基底膜层和平滑肌层厚度。所得结果如下：(1)哮喘模型组血清组胺浓度、气道壁厚度明显高于正常对照组 ({sl P}<0.01) ；哮喘模型延续组明显高于哮喘模型组({sl P}<0.01) ；组胺组明显高于哮喘模型延续组({sl P}<0.01) ；组胺受体拮抗剂组低于哮喘模型延续组({sl P}<0.05, 0.01)。 (2)哮喘模型组PaO_(2)小于正常对照组({sl P}<0.01) ；哮喘模型延续组PaO_(2)、pH、AB、SB小于哮喘模型组({sl P}<0.01)，而PaCO2大于哮喘模型组({sl P}<0.01) ；组胺组PaO_(2)、pH、AB、SB小于哮喘模型延续组({sl P}<0.01)，而PaO_(2)大于哮喘模型延续组({sl P}<0.01) ；组胺受体拮抗剂组PaO_(2)、pH、AB、SB高于哮喘模型延续组({sl P}<0.01)，而PaCO2低于哮喘模型延续组({sl P}<0.01) ；血清Na~(+)、Cl~(-)浓度各组间差异不明显。以上结果提示：(1)组胺在哮喘气道重塑中起介导作用。 (2)应用组胺受体拮抗剂对防治哮喘气道重塑有一定作用。 (3)PaO_(2)、pH与气管、肺门支气管、肺外周小气道气道壁厚度呈负相关({sl P}<0.01)，而PaO_(2)、阴离子间隙(anion gap, AG)值与上述气道壁厚度呈正相关({sl P}<0.01)。

关键词： 组胺; 哮喘; 气道重塑

Role of histamine in airway remodeling of asthmatic guinea pig

Wang Xianghong, Liu Shengyuan, Chen Baosheng, Yu Shangbin, Ye Shiqiao, Chen Qiling

Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology.Wuhan 430030,Hubei；China

Abstract

To investigate the role of histamine in airway remodeling, 50 healthy guinea pigs were divided into 5 groups: control group: nebulized inhalation of distilled water for 8 weeks; asthma model group: nebulized inhalation of ovalbumin (OVA) for 8 weeks after sensitization; continued asthma model group: nebulized inhalation of OVA for 14 weeks after sensitization; histamine group: nebulized inhalation of OVA for 14 weeks after sensitization and histamine was added in the last 6 weeks; antagonist group: nebulized inhalation of OVA for 14 weeks after sensitization and histamine receptor antagonists were added in the last 6 weeks. For each group, the concentration of histamine, sodium ion (Na~(+)), chlorine ion (Cl~(-)), arterial partial pressure of oxygen (PaO_(2)), arterial partial pressure of carbon dioxide (PaO_(2)), pH, actual bicarbonate (AB), standard bicarbonate (SB) in serum, and thickness of airway mucosa, base membrane and smooth muscle were measured and compared with each other. The results showed that: (1) the concentration of histamine in serum and the thickness of airway increased, the following order was, the control group, the asthma model group, the continued asthma model group and histamine group (P<0.01); and the concentration of histamine in serum and the thickness of airway of antagonist group was lower than that of the continued asthma model group (P<0.05, 0.01). (2) PaO_(2) of the asthma model group was lower than that of the normal control group (P<0.01); PaO_(2), pH, AB, SB decreased, the following order was, the asthma model group, the continued asthma model group and the histamine group (P<0.01); and PaO_(2), pH, AB, SB of the antagonist group was higher than that of the continued asthma model group (P<0.01); but for PaO_(2), the order was converse (P<0.01); For the concentration of Na~(+) and Cl~(-) in serum, there was no difference among these groups. It is concluded that: (1) Histamine is one of the mediators in the airway remodeling of asthma. (2) Histamine receptor antagonists may play a role in preventing and treating airway remodeling. (3) There is a negative correlation between the PaO_(2), pH and the wall thickness of the airway (P<0.01), while a positive correlation between the PaO_(2), anion gap (AG) and the wall thickness of the airway (P<0.01).

Key words: Histamine;Asthma;Airway remodeling

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引用本文：

王向红, 刘声远, 陈宝生, 余上斌, 叶仕乔, 陈琪玲. 组胺在哮喘豚鼠气道重塑中的作用 [J]. 生理学报 2005; 57 (6): .

Wang Xianghong, Liu Shengyuan, Chen Baosheng, Yu Shangbin, Ye Shiqiao, Chen Qiling. Role of histamine in airway remodeling of asthmatic guinea pig . Acta Physiol Sin 2005; 57 (6): (in Chinese with English abstract).