1 Department of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, Liaoning, People's Republic of China.
2 The People's Procuratorate of Liaoning Province Judicial Authentication Center, Shenyang, Liaoning, People's Republic of China.
Hum Exp Toxicol. 2019 Jul;38(7):794-802. doi: 10.1177/0960327119842633. Epub 2019 Apr 12.
Paraquat (PQ) is a highly toxic herbicide to humans. Pulmonary fibrosis is one of the most typical features of PQ poisoning, which develops from several days to weeks after ingestion. However, the mechanism of fibrosis is still unclear. In this study, we aimed to determine expressions of autophagy-related markers Beclin 1, microtubule-associated protein light chain 3 (LC3), and p62 in PQ-poisoned lungs and to explore the role of autophagy in pulmonary fibrosis induced by PQ. We detected markers of lung fibrosis and expressions of autophagy-related protein in the specimens from eight fatal cases of PQ poisoning by hematoxylin and eosin staining, Masson's trichrome staining, and immunohistochemistry. Based on the staining results of lung fibrosis, these cases were divided into two groups, fibrosis and non-fibrosis groups. The correlation between autophagy protein expressions and pulmonary fibrosis was examined. The results demonstrated that the autophagy-related proteins were significantly expressed in fibrosis group compared with the non-fibrosis group. There was a significantly positive correlation between these protein expressions and severity of lung fibrosis. In conclusion, autophagy dysfunction may be involved in lung fibrogenesis caused by PQ poisoning. This may be a promising clue for understanding the molecular mechanism underlying PQ-induced lung fibrosis and provide evidence for treating fibrosis by regulating the level of autophagy.
百草枯（PQ）对人类具有高度毒性。肺纤维化是 PQ 中毒的最典型特征之一，在摄入后数天至数周发展。然而，纤维化的机制仍不清楚。在本研究中，我们旨在确定自噬相关标志物 Beclin 1、微管相关蛋白轻链 3（LC3）和 p62 在 PQ 中毒肺中的表达，并探讨自噬在 PQ 诱导的肺纤维化中的作用。我们通过苏木精和伊红染色、马松三色染色和免疫组织化学检测了 8 例致命性 PQ 中毒患者标本中的肺纤维化标志物和自噬相关蛋白的表达。基于肺纤维化的染色结果，将这些病例分为纤维化组和非纤维化组。检查了自噬蛋白表达与肺纤维化之间的相关性。结果表明，纤维化组自噬相关蛋白的表达明显高于非纤维化组。这些蛋白表达与肺纤维化的严重程度呈显著正相关。总之，自噬功能障碍可能参与了 PQ 中毒引起的肺纤维化发生。这可能是理解 PQ 诱导的肺纤维化分子机制的一个有希望的线索，并为通过调节自噬水平治疗纤维化提供证据。
