Folkesson H G, Weström B R, Dahlbäck M, Lundin S, Karlsson B W
Department of Animal Physiology, University of Lund, Sweden.
Exp Lung Res. 1992 Sep-Oct;18(5):595-614. doi: 10.3109/01902149209031697.
The passage of the protein marker, bovine serum albumin (BSA, MW = 67,000), and the nona-peptide, 1-deaminocysteine-8-D-arginine vasopressin (dDAVP, MW = 1067), from the respiratory tract into the blood when applied as an aerosol with a MMAD of 1.7 microns was studied in 14-, 30-, and 100-120-day-old (adult) healthy rats and in adult rats with lung injury. In blood serum of adult rats the levels of immunoreactive BSA reached its maximum 16-24 h after a 1-h aerosol exposure with a calculated total passage of 6.4 +/- 1.8% of the given dose. dDAVP serum levels measured by RIA peaked after 0.5-1 h, giving a total passage of 84.3 +/- 12.9%. With increasing exposure periods from 0.5 to 3 h, which thereby increased the lung burden, the serum levels of BSA and dDAVP increased linearly indicating passive transepithelial transport processes for both molecules. For the young rats, similar serum level-time curves were obtained like those of the adult, with similar total passages of BSA, 4.6 +/- 0.8% for the 14-day-old rats and 5.2 +/- 1.6% for the 30-day-old rats. For dDAVP the total passage was significantly lower in both the 14-day-old rats, 40.9 +/- 12.1%, and the 30-day-old rats, 16.7 +/- 6.1% (p less than .05), as compared to the adult rats. Acute lung inflammation induced in rats by intratracheal instillation of 5 mg ferritin/kg body wt prior to a 1-h marker aerosol exposure increased the passage of BSA (58.7 +/- 18.8%, p less than .05), while the dDAVP passage was less affected (99.2 +/- 25.2%, p greater than .05) as compared to the healthy adult rats. The results indicate that after aerosol exposure the total passage of dDAVP over the respiratory tract was higher than that of the macromolecule BSA, the passage appeared to increase with the maturity of the rats and by inflammatory changes in the lung tissue.
将蛋白质标志物牛血清白蛋白(BSA,分子量 = 67,000)和九肽1 - 脱氨基半胱氨酸 - 8 - D - 精氨酸加压素(dDAVP,分子量 = 1067)以质量中值空气动力学直径(MMAD)为1.7微米的气雾剂形式应用于14日龄、30日龄和100 - 120日龄(成年)健康大鼠以及成年肺损伤大鼠,研究其从呼吸道进入血液的情况。在成年大鼠血清中,免疫反应性BSA水平在1小时气雾剂暴露后16 - 24小时达到峰值,计算得出给定剂量的总通过率为6.4±1.8%。通过放射免疫分析(RIA)测定的dDAVP血清水平在0.5 - 1小时后达到峰值,总通过率为84.3±12.9%。随着暴露时间从0.5小时增加到3小时,从而增加了肺部负担,BSA和dDAVP的血清水平呈线性增加,表明这两种分子均通过被动跨上皮转运过程。对于幼鼠,获得了与成年大鼠相似的血清水平 - 时间曲线,BSA的总通过率相似,14日龄大鼠为4.6±0.8%,30日龄大鼠为5.2±1.6%。对于dDAVP,14日龄大鼠和30日龄大鼠的总通过率均显著低于成年大鼠,分别为40.9±12.1%和16.7±6.1%(p<0.05)。在1小时标志物气雾剂暴露前经气管内注入5mg铁蛋白/kg体重诱导大鼠急性肺部炎症,与健康成年大鼠相比,增加了BSA的通过率(58.7±18.8%,p<0.05),而dDAVP的通过率受影响较小(99.2±25.2%,p>0.05)。结果表明,气雾剂暴露后,dDAVP在呼吸道的总通过率高于大分子BSA,通过率似乎随着大鼠成熟度以及肺组织炎症变化而增加。