摘要目的 探讨组胺H3受体激动剂IMETIT对变应性鼻炎(allergic rhinitis,AR)豚鼠模型P物质(substance P,SP)及其受体(substance P receptor,SP-R)mRNA表达的影响.方法 36只清洁级豚鼠以随机数字表法分为4组,每组9只,分别为:AR模型无干预组(A组)、IMETIT干预组(B组)、组胺H1受体拮抗剂氯雷他定干预组(c组)、IMETIT联合氯雷他定干预组(D组).4组豚鼠均以卵清蛋白(ovalbumin,OVA)为致敏原,建立豚鼠AR模型,观察豚鼠30 min内喷嚏、抓鼻次数,呼吸频率及鼻黏膜病理变化.以免疫组化法检测鼻中隔黏膜中每个高倍镜视野(high power,HP)下SP阳性细胞数,以反转录-聚合酶链反应(reverse transcriptive-polymerase chain reaction,RT-PCR)测定鼻中隔黏膜中SP-R mRNA的相对表达量.采用SPSS 13.0软件对数据进行分析.结果 B组平均((x)±s,下同)喷嚏[(15.0±1.3)次]、抓鼻[(16.5±2.3)次]、呼吸频率[(76.3±4.1)次/min]较A组[分别为(23.5±2.6)次、(26.1±4.1)次和(66.5±5.8)次/min)]明显改善,差异有统计学意义(P值分别为0.000、0.000和0.001);B组SP阳性细胞数为(11.6±3.6)个/HP,SP-R mRNA的相对表达量为(0.64±0.04),较A组[分别为(27.1±9.7)个/HP、(0.83±0.03)]明显减少,差异有统计学意义(P值分别为0.000、0.000).D组喷嚏[(10.0±2.3)次]、抓鼻[(11.8±1.7)次]、呼吸频率[(90.0±5.0)次/min]与B组比较亦显著改善,差异有统计学意义(P值分别为0.000、0.002和0.000);D组SP阳性细胞数[(2.0±1.7)个/HP)]及SP-R mRNA的相对表达量(0.52±0.06)较B组亦明显减少(P值分别为0.012、0.000).B组、D组较A组豚鼠鼻黏膜病理改变减轻.析因分析显示,IMETIT联合氯雷他定对上述影响具有协同作用(F值分别为11.59、8.28、5.61、5.48、6.50,P值分别为0.002、0.008、0.025、0.027、0.017).结论 IMETIT以及IMETIT联合氯雷他定能缓解豚鼠AR的症状.IMETIT可以减少鼻黏膜中SP阳性细胞数量同时降低SP-R mRNA的表达.IMETIT和氯雷他定具有协同作用.

abstractsObjective To explore the influence of histamine H3 receptor agonist, IMETIT and simultaneous use of IMETIT and H1-receptor antagonist, Loratadine, on the symptoms of allergic rhinitis (AR) and substance P(SP) secretion and expression of SP receptor (SP-R)mRNA in AR model in guinea pigs. Methods Guinea pigs were divided randomly into 4 groups: AR group (group A) , IMETIT group (group B), Loratadine group (group C) and IMETIT + Loratadine group (group D). The severity of AR was assessed by determining the extent of three markers of allergic symptoms (sneezing, nasal rubbing and nose blocking). The changes in the nasal mucosa were studied by pathological methods. The expression of positive cell of SP was detected by immunohistochemistry. SP-R mRNA expression in nasal mucosa was used to do reverse transcriptive-polymerase chain reaction (RT-PCR). Statistical analysis was performed using a SPSS 13. 0 software. Results In Group B, the mean (i ± s) number of sneeze [ (15. 0 ± 1. 3) times] , scratching nose [ ( 16. 5 ± 2. 3 ) times ] and respiratory frequency [ (76. 3 ± 4. 1 ) times/min ] were significantly improved than those in group A [ (23. 5 ±2. 6) times, (26. 1 ±4. 1) times and (66. 5 ±5. 8) times/min, respectively), P value were 0.000, 0.000 and 0.001, respectively]. The numbers of SP positive cells [(11. 6 ±3. 6)/HP] and SP-R mRNA expression (0.64 ±0.04 ) in group B were reduced significantly compared to group A [ (27. 1 ± 9. 7)/HP, (0. 83 ± 0. 03 ) , P value were 0. 000, 0. 000, respectively]. Sneeze [(10.0 ±2.3) times], scratching nose [(11.8 ± 1.7) times] and respiration [ (90. 0 ±5. 0) times/min] in Group D were improved significantly than those in group B (P value were 0.000, 0. 002 and 0. 000, respectively). SP-positive cells [ (2. 0 ± 1. 7)/HP] and SP-R mRNA expression (0. 52 ±0. 06) in Group D compared with group B were also significantly reduced (P value were 0. 012 and 0. 000, respectively). Pathological changes in guinea pig nasal mucosa in group B, group D were alleviated than those in group A. The combination of IMETIT and Loratadine had a synergistic effect on these effects (F value were 11. 59, 8. 28,5. 61,5.48,6. 50, respectively, P value were 0. 002, 0. 008, 0. 025, 0. 027, 0. 017). Conclusions IMETIT and the combination of IMETIT with Loratadine can effectively relieve the symptoms of AR in guinea pigs, its mechanism may be relevant to reduce SP secretion and the expression of SP-RmRNA, and the two has a synergistic effect. It may be useful as a novel therapeutic approach in nasal allergy.