气道高反应中血管活性肠肽及受体的时空分布

目的　探讨血管活性肠肽 (VIP)在气道高反应性形成过程中的作用。方法　 2 5只新西兰兔按随机数字表法分为 5组 ,每组 5只 ,分别为非应激对照组 (A组 )和臭氧攻击第 1天组 (B0组 )、第 2天组 (B1组 )、第 4天组 (B2 组 )、第 8天组 (B3 组 ) ,每天 1h。用放射免疫法检测肺组织匀浆中VIP含量 ,逆转录 聚合酶链反应 (RT PCR)测定肺内VIP受体 1(VIPR1)mRNA表达 ,并用原位杂交法观察VIPR1mRNA阳性细胞在肺内分布。结果　 ( 1)随臭氧应激时间延长 ,肺组织匀浆中VIP浓度逐渐增高 ,于第 4天达峰值 ,之后逐渐下降 ,第 8天降至正常水平 ;( 2 )肺组织匀浆中VIPR1mRNA表达也呈先增加后降低的双向变化 ,随应激时间的延长 ,表达逐渐增强 ,应激第 2～ 4天达到峰值 ,之后逐渐下降 ,应激第 8天降至正常水平 ;( 3)A组肺间质、支气管上皮细胞、血管内皮细胞、平滑肌细胞均有VIPR1mRNA表达 ,分布均匀。应激第 2～ 4天 ,阳性细胞呈斑片状集中于气管、血管周围染色强度增加 ,肺泡腔内亦可见阳性染色细胞 ,至臭氧应激第 8天 ,阳性染色细胞减少。结论　VIP由VIPR1介导参与气道高反应性形成

The temporal and spatial distribution of vasoactive intestinal peptide and its receptor in the development of airway hyperresponsiveness

Objective To determine the possible involvement of vasoactive intestinal peptide(VIP) in the development of airway hyperresponsiveness(AHR) Methods Twenty five rabbits were randomly divided into five groups(5 animals each) Four groups were exposed to 2 0 ppm ozone 1 h/day for 1(group B 0),2(group B 1),4(group B 2),and 8(group B 3) days, respectively The control group(group A) breathed only filtered room air The changes of the VIP level and the mRNA expression of VIP receptor 1(VIPR1) in the lung were detected at various ozone stressing time points In situ hybridization was performed to examine the distribution of VIPR1 in the lung Results (1)The concentration of VIP in the lung increased slowly and were maximal at day 4, then returned to the normal level (2)The changing pattern of the VIPR1 mRNA in the lung was similar to those observed for VIP Increases in VIPR1 mRNA were detectable by 1 day and maximal by 2 4 days, and then decreased slowly (3)In group A,VIPR1 was expressed on airway epithelium, in pulmonary interstitial and focal areas of airways and vascular smooth muscles By days 2 to 4,hybridization staining increased and the majority of VIPR1 positive cells was located in the perivascular and peribronchiolar area On day 8, very few positive cells were seen in the lung Conclusion VIP may play an important role in the development of AHR by binding with VIPR1