Cantor J O, Cerreta J M, Armand G, Turino G M
St. Luke's-Roosevelt Institute for Health Sciences, New York, New York 10019, USA.
Proc Soc Exp Biol Med. 1998 Apr;217(4):471-5. doi: 10.3181/00379727-217-44260.
This laboratory has previously shown that an intratracheally instilled solution of hyaluronic acid (HA) protects the lung from elastase-induced airspace enlargement. In those studies, fluorescein-labeled HA was found to bind preferentially to lung elastic fibers, suggesting a mechanism for the protective effect. The current investigation extends these findings by examining the capacity of an aerosol preparation of HA to similarly inhibit elastase-induced lung injury. Syrian hamsters were exposed to aerosolized bovine tracheal HA (0.1% solution in water) for either 25 or 50 min, then immediately instilled intratracheally with 80 units of human neutrophil elastase. One week later the lungs were examined for airspace enlargement, using the mean linear intercept method. Animals exposed to HA for 50 min showed a significant decrease in airspace enlargement compared to controls exposed to aerosolized water alone (68.2 microm vs 85.9 microm; P < 0.05). The 25-min exposure to the HA aerosol also reduced the mean linear intercept compared to controls (73.7 microm vs 85.9 microm), but this decrease was not statistically significant. With regard to possible inflammatory effects of HA, there was no difference in the percentage of lavaged neutrophils between HA-treated and control lungs at 24 hr (1.4% vs 1.8%, respectively). As with earlier experiments using intratracheally instilled HA, aerosolized fluorescein-labeled HA was found to bind to lung elastic fibers. These results suggest that aerosolized HA may prevent elastase-mediated injury in pulmonary emphysema.
本实验室先前已表明，经气管内注入的透明质酸（HA）溶液可保护肺部免受弹性蛋白酶诱导的气腔扩大。在这些研究中，发现荧光素标记的HA优先与肺弹性纤维结合，提示了其保护作用的机制。当前的研究通过检查HA气雾剂抑制弹性蛋白酶诱导的肺损伤的能力来扩展这些发现。将叙利亚仓鼠暴露于雾化的牛气管HA（0.1%水溶液）中25或50分钟，然后立即经气管内注入80单位的人中性粒细胞弹性蛋白酶。一周后，使用平均线性截距法检查肺部气腔扩大情况。与仅暴露于雾化水的对照组相比，暴露于HA 50分钟的动物气腔扩大明显减少（分别为68.2微米和85.9微米；P<0.05）。与对照组相比，暴露于HA气雾剂25分钟也降低了平均线性截距（分别为73.7微米和85.9微米），但这种降低无统计学意义。关于HA可能的炎症作用，HA处理组和对照组在24小时时灌洗中性粒细胞的百分比无差异（分别为1.4%和1.8%）。与早期使用经气管内注入HA的实验一样，发现雾化的荧光素标记的HA与肺弹性纤维结合。这些结果表明，雾化的HA可能预防肺气肿中弹性蛋白酶介导的损伤。
