Effect of Different Molecular Weights of Polyacrylic Acid on Rat Lung Following Intratracheal Instillation

不同分子量聚丙烯酸气管内滴注对大鼠肺组织的影响

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作者:Chinatsu Nishida, Hiroto Izumi, Taisuke Tomonaga, Ke-Yong Wang, Hidenori Higashi, Jun-Ichi Takeshita, Ryohei Ono, Kazuki Sumiya, Shota Fujii, Yuki Hata, Kazuo Sakurai, Yasuyuki Higashi, Kei Yamasaki, Kazuhiro Yatera, Yasuo Morimoto

Background

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.

Conclusion

HMW PAA induced persistence of lung disorder, suggesting that molecular weight is a physicochemical characteristic of PAA-induced lung disorder.

Methods

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.

Results

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.

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