Horan K L, Adamski S W, Ayele W, Langone J J, Grega G J
Am J Pathol. 1986 Jun;123(3):570-6.
The aim of this study was to determine whether histamine-stimulated increases in macromolecular efflux are dependent on the formation of specific vascular leakage sites, or whether other mechanisms need to be invoked to explain the increase in macromolecular efflux produced by this inflammatory mediator. Intravital light microscopy was used to localize and quantitate vascular macromolecular leakage sites in the noneverted hamster cheek pouch. Fluorimetric measurements of plasma and suffusate tracer (FITC-D 70,000 mol wt) concentrations were utilized to quantitate changes in macromolecular efflux. In some experiments, the FITC-D was injected intravenously either at the start of or after the start of a prolonged histamine suffusion for estimation of the duration of the vascular FITC-D leakage response. In saline control cheek pouches there were few, if any, visible FITC-D vascular leakage sites and only small increases in the [FITC-D]s. The arteriolar vasodilators papaverine (1 X 10(-5) M) and isoproterenol (1 X 10(-5) M) failed to increase the formation of vascular FITC-D leakage sites, and the magnitude of the increase in [FITC-D]s produced by these agents was similar to that observed in saline controls. Histamine (1 X 10(-5) M) suffused for either 15, 60, or 120 minutes produced marked increases in [FITC-D]s and in the number of venular FITC-D leakage sites. The venular FITC-D leakage sites began to fade after 10-20 minutes, eventually disappearing altogether. In contrast, the [FITC-D]s was markedly increased throughout the 120-minute observation period. Treatment with papaverine prior to and during the 60-minute histamine suffusion failed to prevent the mediator-stimulated vascular leakage response. In contrast, similar treatment with isoproterenol inhibited the histamine-stimulated increases in [FITC-D]s and the formation of venular FITC-D leakage sites. When the tracer was injected intravenously at the start of the 60-minute histamine suffusion (1 X 10(-5) M), the [FITC-D]s and the number of vascular leakage sites were markedly increased. However, when the tracer was injected intravenously 30 minutes after the start of the 60-minute histamine suffusion, there were only minimal increases in [FITC-D]s and the formation of venular leakage sites. These findings suggest that prolonged suffusions of histamine produce transient increases in macromolecular efflux which are dependent on the formation of discrete venular macromolecular leakage sites.(ABSTRACT TRUNCATED AT 400 WORDS)
本研究的目的是确定组胺刺激引起的大分子外流量增加是否依赖于特定血管渗漏部位的形成，或者是否需要借助其他机制来解释这种炎症介质所产生的大分子外流量增加。采用活体光学显微镜对未翻转的仓鼠颊囊中的血管大分子渗漏部位进行定位和定量。利用荧光法测量血浆和灌洗液中示踪剂（分子量70,000的异硫氰酸荧光素 - D）的浓度，以定量大分子外流量的变化。在一些实验中，在长时间组胺灌注开始时或开始后静脉注射异硫氰酸荧光素 - D，以估计血管异硫氰酸荧光素 - D渗漏反应的持续时间。在生理盐水对照的颊囊中，几乎没有可见的异硫氰酸荧光素 - D血管渗漏部位，并且[异硫氰酸荧光素 - D]s仅有小幅增加。小动脉血管舒张剂罂粟碱（1×10⁻⁵ M）和异丙肾上腺素（1×10⁻⁵ M）未能增加血管异硫氰酸荧光素 - D渗漏部位的形成，并且这些药物所产生的[异硫氰酸荧光素 - D]s增加幅度与生理盐水对照组中观察到的相似。组胺（1×10⁻⁵ M）灌注15、60或120分钟导致[异硫氰酸荧光素 - D]s以及小静脉异硫氰酸荧光素 - D渗漏部位数量显著增加。小静脉异硫氰酸荧光素 - D渗漏部位在10 - 20分钟后开始消退，最终完全消失。相比之下，在整个120分钟观察期内[异硫氰酸荧光素 - D]s显著增加。在60分钟组胺灌注之前和期间用罂粟碱处理未能阻止介质刺激的血管渗漏反应。相比之下，用异丙肾上腺素进行类似处理可抑制组胺刺激的[异硫氰酸荧光素 - D]s增加以及小静脉异硫氰酸荧光素 - D渗漏部位的形成。当在60分钟组胺灌注（1×10⁻⁵ M）开始时静脉注射示踪剂时，[异硫氰酸荧光素 - D]s和血管渗漏部位数量显著增加。然而，当在60分钟组胺灌注开始30分钟后静脉注射示踪剂时，[异硫氰酸荧光素 - D]s仅有极小增加，并且小静脉渗漏部位的形成也很少。这些发现表明，长时间灌注组胺会导致大分子外流量短暂增加，这依赖于离散的小静脉大分子渗漏部位的形成。（摘要截短至400字）
