【摘要】 <正> 药物通过呼吸进行吸收的路径依次为气管→支气管→肺泡,其中通过肺泡上皮细胞吸收占90％以上。由于肺泡上皮细胞使大分子的蛋白多肽类药物不易通过,是它们渗透的主要屏障,因此对肺泡膜屏障特性、药物透过过程及渗透特性的研究有助于更更多还原

【Abstract】 Aim An in vitro cultured monolayer system of alveolar epithelial cells was used as a model toinvestigate the transport pathway peptides or proteins, salmon calcitonin （sCT）, insulin （INS）, recombinanthirudin （rHAV2）, and recombinant human growth hormone （rhGH）, in pulmonary epithelium in vivo.Methods Human lung adenocarcinoma A549 cells formed continuous monolayers with growing polycarbonatefilters of Transwell plate. Transport studies of macromolecules in the monolayer system were carried out ’after 6days in culture, The transport of peptides or proteins with MW 3 400-22 000 was studied in cultured humanlung adenocarcinoma A549 cell monolayers at different conditions. Results The results showed that theapparent permeability coefficients （Papp） of these macromolecules across A549 cell monolayers ranged from2×10^-6 to 5×10^-6 cm’s^-1 and exhibited good inverse correlation with molecule weight. No concentration,direction and temperature dependence were observed in the permeation of sCT, INS and rHAV2. While the Pappof rhGH in the BA direction (2.25×10^-6 cm’s^-1) was significantly less than that in the reverse direction. ThePapp values of rhGH were concentration and temperature independent in the AB direction. Conclusion Thesefindings suggest that the hydrophilic peptides and proteins, salmon calcitonin, insulin, recombinant hirudin,and recombinant human growth hormone used in this study, appeared to penetrate the A549 cell monolayers viaa paracellular pathway by passive diffusion mechanism.更多还原