聚苯乙烯微塑料暴露通过促进库普弗细胞焦亡加剧急性肝损伤。
Polystyrene microplastics exposure aggravates acute liver injury by promoting Kupffer cell pyroptosis.
机构信息
Department of Pharmacy, Shanghai Baoshan Luodian Hospital, Shanghai, China.
Department of Pharmacy, Suining Branch of the Hospital Affiliated to Xuzhou Medical University, Suining, China.
出版信息
Int Immunopharmacol. 2024 Jan 5;126:111307. doi: 10.1016/j.intimp.2023.111307. Epub 2023 Nov 29.
OBJECTIVE
To investigate the long-term effects of polystyrene (PS) exposure on acute liver injury.
METHODS
The carbon tetrachloride-induced acute injury mouse model was subjected to long-term PS exposure. Pyroptosis was inhibited by knocking out Gsdmd in mice or treating with the Gsdmd inhibitor necrosulfonamide (NSA) to evaluate the effect of PS on liver injury. Kupffer cells were used as a cellular model to examine the effects of PS on cell pyroptosis, lactate dehydrogenase release rate, structural integrity (propidium iodide staining), and inflammatory factor levels.
RESULTS
In mice, PS exposure exacerbated acute liver injury, which was mitigated upon Gsdmd knockout (KO) or NSA treatment along with the downregulation of tissue inflammatory response. In vitro studies demonstrated that PS promoted Kupffer cell pyroptosis, which was suppressed upon Gsdmd KO or NSA treatment along with the alleviation of inflammation.
CONCLUSION
These results suggest that long-term PS exposure exacerbates acute liver injury by promoting Kupffer cell pyroptosis, which is one of the hepatotoxic mechanisms of PS.
目的
研究聚苯乙烯（PS）暴露对急性肝损伤的长期影响。
方法
采用四氯化碳诱导的急性损伤小鼠模型进行长期 PS 暴露。通过敲除 Gsdmd 或用 Gsdmd 抑制剂坏死磺酰胺（NSA）处理来抑制细胞焦亡，以评估 PS 对肝损伤的影响。用枯否细胞作为细胞模型，检测 PS 对细胞焦亡、乳酸脱氢酶释放率、结构完整性（碘化丙啶染色）和炎症因子水平的影响。
结果
在小鼠中，PS 暴露加重了急性肝损伤，而 Gsdmd 敲除（KO）或 NSA 处理减轻了组织炎症反应。体外研究表明，PS 促进了枯否细胞的焦亡，而 Gsdmd KO 或 NSA 处理减轻了炎症，从而抑制了焦亡。
结论
这些结果表明，长期 PS 暴露通过促进枯否细胞焦亡加重急性肝损伤，这是 PS 的一种肝毒性机制。
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