Cantor J O, Cerreta J M, Armand G, Keller S, Turino G M
Columbia University College of Physicians and Surgeons, New York, NY.
Exp Lung Res. 1993 Mar-Apr;19(2):177-92. doi: 10.3109/01902149309031718.
Although emphysema is generally characterized by damage to pulmonary elastic fibers, the causes of such injury appear to be complex and are not entirely explained by a singular imbalance between elastases and their inhibitors. Other factors could compromise elastic fiber integrity. To test the validity of this argument, hamsters were instilled intratracheally with a nonelastolytic enzyme, hyaluronidase (which reduces lung hexuronic acid content by 21% after 24 h), then exposed to an otherwise nontoxic concentration of oxygen (60%) for 4 days. Additional groups were given (1) hyaluronidase and room air, (2) saline and 60% oxygen, and (3) saline and room air. Treatment with both hyaluronidase and 60% oxygen resulted in a significant increase in air-space enlargement at 4 days (67.1 vs. 57.9 microns for saline/room air controls; p < .05), which was accompanied by only minimal inflammatory changes, as determined by both light microscopy and lavage cytology. Animals receiving either hyaluronidase or 60% oxygen alone showed no significant increases in air-space size compared to those given saline and exposed to room air. While the mechanisms responsible for these results are unclear, the marked increase in radiolabeling of lung elastin cross-links (desmosine and isodesmosine) in animals receiving both hyaluronidase and 60% oxygen (429 vs. 168 cpm/g dry lung for saline/room air controls; p < .05), as well as a significant decrease in total lung desmosine and isodesmosine (32.5 vs. 37.7 micrograms/lung for saline/room air controls; p < .05), suggests that elastic fiber damage is a potential factor. Moreover, only those animals receiving both hyaluronidase and 60% oxygen showed a significant rise in cell-free elastase activity in lavage fluids compared to saline/room air controls (83.3 vs. 48.3 ng; p < .05). On the basis of these findings, it is concluded that while elastic fiber damage may be a common pathway in emphysema, the factors that initiate the disease may be more varied than previously suspected and not always related to the balance between elastases and their inhibitors.
虽然肺气肿通常以肺弹性纤维受损为特征，但这种损伤的原因似乎很复杂，并非完全由弹性蛋白酶与其抑制剂之间的单一失衡来解释。其他因素可能会损害弹性纤维的完整性。为了验证这一观点的正确性，将仓鼠经气管内注入一种非弹性溶解酶——透明质酸酶（24小时后可使肺己糖醛酸含量降低21%），然后让其暴露于原本无毒浓度的氧气（60%）中4天。另外设置了几组仓鼠，分别给予：（1）透明质酸酶并置于室内空气中，（2）生理盐水并给予60%氧气，（3）生理盐水并置于室内空气中。同时给予透明质酸酶和60%氧气处理的仓鼠在4天时气腔扩大显著增加（生理盐水/室内空气对照组为57.9微米，而该组为67.1微米；p<0.05），通过光学显微镜和灌洗细胞学检查确定，此时仅伴有轻微的炎症变化。与给予生理盐水并暴露于室内空气的仓鼠相比，单独接受透明质酸酶或60%氧气处理的动物气腔大小没有显著增加。虽然导致这些结果的机制尚不清楚，但在同时接受透明质酸酶和60%氧气处理的动物中，肺弹性蛋白交联（锁链素和异锁链素）的放射性标记显著增加（生理盐水/室内空气对照组为168 cpm/g干肺，该组为429 cpm/g干肺；p<0.05），同时肺中锁链素和异锁链素的总量显著减少（生理盐水/室内空气对照组为37.7微克/肺，该组为32.5微克/肺；p<0.05），这表明弹性纤维损伤是一个潜在因素。此外，与生理盐水/室内空气对照组相比，只有那些同时接受透明质酸酶和60%氧气处理的动物灌洗液中无细胞弹性蛋白酶活性显著升高（分别为83.3纳克和48.3纳克；p<0.05）。基于这些发现，可以得出结论：虽然弹性纤维损伤可能是肺气肿的一个常见途径，但引发该疾病的因素可能比之前怀疑的更多样化，且并不总是与弹性蛋白酶及其抑制剂之间的平衡有关。
