下丘脑室旁核组胺H_3受体对哮喘大鼠呼吸运动的调节

Effects of histamine H_3 receptors in the hypothalamic paravent ricular nuclei on respiration in rats with asthma

目的:探讨下丘脑室旁核(PVN)组胺H3 受体对哮喘大鼠呼吸运动的影响及其作用机制。方法:将大鼠随机分为对照组、模型组、假手术组、生理盐水组、PVN内微量注射特异性组胺H3 受体激动剂R- (α) - 甲基组胺[(R -(α) - methylhistamine ,R- (α) -MeHA]的R- (α) - MeHA组以及PVN内微量注射组胺H3 受体拮抗剂thioperamide(Thio)的Thio组,采用中枢立体定位技术,在PVN植入带芯的不锈钢外套管,通过内管恒速注射不同药物。用电生理方法记录膈肌肌电活动;用胸内压法测定气道阻力、肺顺应性。结果:与对照组比较,模型组膈肌放电频率增加,膈肌肌电积分幅值下降,气道阻力增加,肺顺应性降低(均为P <0 .0 1)。与生理盐水组比较,R- (α)- MeHA组膈肌放电频率下降(P <0 .0 1) ,膈肌肌电积分幅值增加(P <0 .0 5 ) ,气道阻力降低(P <0 .0 1) ,肺顺应性改善(P <0 .0 1) ;Thio可阻断上述效应,差异均有统计学意义。结论:PVN内组胺H3 受体参与呼吸运动的调节,特异性激动组胺H3 受体能改善哮喘大鼠的肺功能。

Objective To explore the effects and mechanisms of histamine H_3 receptors in the hypothalamic paraventricular nuclei (PVN) on respiration in rats with asthma.Methods Experiments were carried out on 36 rats , which were divided into control group, model group, sham group, NS group, R(α)methylhistamine group and thioperamide group. The drugs were injected (icv) into bilateral PVN, and the diaphragmatic muscle electric activities and pulmonary function were monitored by Powerlab/400 system. Results Compared with control group, the diaphragmatic muscle electric activities and pulmonary function in the model group changed evidently (P<0.01). Compared with NS group, histamine H_3 receptors agonist (R)αmethylhistamine not only obviously lowered the frequency of diaphragmatic electric activity and airway resistance (P<0.01), but also markedly increased integrated diaphragmatic electric activity (P<0.05) and pulmonary compliance (P<0.01). Furthermore, these responses were blocked by thioperamide, an H_3 receptors specific antagonist. Conclusion Specific activation histamine H_3 receptors in PVN improves respiration of rats with asthma.