Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu 807-8555, Fukuoka, Japan.
Department of Occupational Pneumology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu 807-8555, Fukuoka, Japan.
Int J Mol Sci. 2022 Sep 7;23(18):10345. doi: 10.3390/ijms231810345.
We conducted intratracheal instillations of different molecular weights of polyacrylic acid (PAA) into rats in order to examine what kinds of physicochemical characteristics of acrylic acid-based polymer affect responses in the lung.
F344 rats were intratracheally exposed to a high molecular weight (HMW) of 598 thousand g/mol or a low molecular weight (LMW) of 30.9 thousand g/mol PAA at low and high doses. Rats were sacrificed at 3 days, 1 week, 1 month, 3 months and 6 months post exposure.
HMW PAA caused persistent increases in neutrophil influx, cytokine-induced neutrophil chemoattractants (CINC) in the bronchoalveolar lavage fluid (BALF), and heme oxygenase-1 (HO-1) in the lung tissue from 3 days to 3 months and 6 months following instillation. On the other hand, LMW PAA caused only transient increases in neutrophil influx, CINC in BALF, and HO-1 in the lung tissue from 3 days to up to 1 week or 1 month following instillation. Histopathological findings of the lungs demonstrated that the extensive inflammation and fibrotic changes caused by the HMW PAA was greater than that in exposure to the LMW PAA during the observation period.
HMW PAA induced persistence of lung disorder, suggesting that molecular weight is a physicochemical characteristic of PAA-induced lung disorder.
我们通过向大鼠气管内滴注不同分子量的聚丙烯酸（PAA），研究丙烯酸基聚合物的哪些理化特性会影响肺部的反应。
F344 大鼠以低剂量或高剂量经气管内暴露于高分子量（HMW）59.8 万 g/mol 或低分子量（LMW）30.9 万 g/mol 的 PAA。大鼠在暴露后 3 天、1 周、1 个月、3 个月和 6 个月时被处死。
HMW PAA 导致中性粒细胞浸润、支气管肺泡灌洗液（BALF）中细胞因子诱导的中性粒细胞趋化因子（CINC）和肺组织血红素加氧酶-1（HO-1）持续增加，从暴露后 3 天持续到 3 个月和 6 个月。另一方面，LMW PAA 仅导致中性粒细胞浸润、BALF 中的 CINC 和肺组织中的 HO-1 在暴露后 3 天至 1 周或 1 个月内短暂增加。肺部的组织病理学发现，HMW PAA 引起的广泛炎症和纤维化改变大于暴露于 LMW PAA 期间的观察期。
HMW PAA 诱导肺部疾病持续存在，提示分子量是 PAA 诱导肺部疾病的理化特性之一。
