速激肽诱导的未成熟气道气流阻塞和微血管渗漏的减轻

Attenuation of tachykinin-induced airflow obstruction and microvascular leakage in immature airways.

作者信息

Tokuyama K, Yokoyama T, Morikawa A, Mochizuki H, Kuroume T, Barnes P J

机构信息

Department of Pediatrics, Gunma University School of Medicine, Maebashi, Japan.

出版信息

Br J Pharmacol. 1993 Jan;108(1):23-9. doi: 10.1111/j.1476-5381.1993.tb13434.x.

DOI:10.1111/j.1476-5381.1993.tb13434.x

PMID:7679033

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1907718/

Abstract

To study the effect of maturation on substance P (SP)- and neurokinin A (NKA)-induced airflow obstruction and airway microvascular leakage (MVL), we have measured changes in both lung resistance (RL) and extravasation of Evans blue dye in anaesthetized immature (aged 14 +/- 1 days) and adult guinea-pigs (aged 80 +/- 3 days). 2. RL and its recovery after hyperinflation at 5 min were measured for 6 min after i.v. SP (0.2, 1 and 30 nmol kg-1), NKA (1 and 10 nmol kg-1) or vehicle (0.9% NaCl). After measurement of RL, MVL in trachea, main bronchi and intrapulmonary airways was also examined. 3. The order of potency in inducing airflow obstruction did not change with age (NKA > SP) but immature animals required a larger dose of SP or NKA than adults to cause a significant increase in RL. 4. The order of potency in inducing airway microvascular leakage was SP > NKA in both immature and adult animals. The amount of extravasated dye after SP was significantly less in immature airways, especially in central airways. 5. Phosphoramidon (2.5 mg kg-1), a neutral endopeptidase (NEP) inhibitor, significantly increased RL after 0.2 nmol kg-1 SP only in adult airways. Phosphoramidon enhanced the dye extravasation after 0.2 nmol kg-1 SP in both immature and adult airways with a significantly greater amount of dye in adult animals, suggesting that mechanisms other than changes in NEP activity may be responsible for this age-related difference. 6. RL after hyperinflation following SP was not correlated with the degree of extravasation of Evans blue dye in immature animals, whereas it was closely correlated in adult animals. 7. SP and NKA may be less potent in causing both bronchoconstriction and microvascular leakage in immature airways. 8. Airway oedema caused by microvascular leakage may contribute less in immature airways to airflow obstruction after SP or NKA.

摘要

为研究成熟对P物质（SP）和神经激肽A（NKA）诱导的气流阻塞及气道微血管渗漏（MVL）的影响，我们测量了麻醉状态下未成熟豚鼠（年龄14±1天）和成年豚鼠（年龄80±3天）的肺阻力（RL）变化以及伊文思蓝染料的外渗情况。2. 在静脉注射SP（0.2、1和30 nmol·kg⁻¹）、NKA（1和10 nmol·kg⁻¹）或溶媒（0.9%氯化钠）后，测量6分钟内的RL及其在5分钟过度充气后的恢复情况。在测量RL后，还检测了气管、主支气管和肺内气道的MVL。3. 诱导气流阻塞的效力顺序不随年龄变化（NKA＞SP），但未成熟动物比成年动物需要更大剂量的SP或NKA才能使RL显著增加。4. 在未成熟和成年动物中，诱导气道微血管渗漏的效力顺序均为SP＞NKA。SP作用后，未成熟气道尤其是中央气道的染料外渗量明显较少。5.磷酰胺脒（2.5 mg·kg⁻¹），一种中性内肽酶（NEP）抑制剂，仅在成年气道中，在0.2 nmol·kg⁻¹ SP注射后显著增加RL。磷酰胺脒在未成熟和成年气道中均增强了0.2 nmol·kg⁻¹ SP后的染料外渗，成年动物中的染料量显著更多，这表明除NEP活性变化外的其他机制可能是造成这种年龄相关差异的原因。6. 在未成熟动物中，SP后过度充气后的RL与伊文思蓝染料的外渗程度不相关，而在成年动物中则密切相关。7. SP和NKA在引起未成熟气道的支气管收缩和微血管渗漏方面可能效力较低。8. 微血管渗漏引起的气道水肿在未成熟气道中对SP或NKA后的气流阻塞贡献可能较小。