目的 考察对乙酰氨基酚对Lewis肺癌荷瘤小鼠上皮屏障功能的影响，为临床合理用药提供参考。方法 C57BL/6小鼠的右腋处皮下接种2×10⁶个Lewis肺癌细胞，通过小鼠一般状态和肺组织表面转移灶考察对乙酰氨基酚对肿瘤肺转移的影响。利用病理组织形态、HE染色、免疫组化等方法检测肿瘤转移情况，同时采用qRT-PCR法检测屏障相关蛋白Claudin 5、Occludin、ZO-1、DSG2 mRNA表达水平，探讨对乙酰氨基酚影响上皮屏障的潜在机制。结果 与对照组和模型组比较，大体形态观察对乙酰氨基酚组小鼠肺组织出现了明显的肿瘤转移灶，病理及免疫组织化学染色结果进一步显示对乙酰氨基酚组肺组织转移灶明显增加，qRT-PCR结果显示对乙酰氨基酚组小鼠肺组织Claudin 5、Occludin、ZO-1、以及DSG2等屏障相关蛋白mRNA表达均显著降低。结论 对乙酰氨基酚可以影响上皮屏障相关蛋白表达诱导上皮屏障功能障碍，并可能继而有利于肿瘤转移。

Objective To explore the barrier dysfunction induced by acetaminophen, and provide guidance for the clinical rational use of drugs. Methods 2×10⁶ Lewis lung cancer cells were subcutaneously tumor-bearing in the right axillary of C57BL/6 mice. The general states of the mice were observed, and the tumor metastasis were detected by pathological morphology, HE and immunohistochemistry. At the same time, mRNA expression levels of barrier related proteins were detected by qRT-PCR, to explore the potential mechanism of acetaminophen affecting epithelial barrier.Results Compared with control and model groups, the lung tissue of mice in acetaminophen group showed obvious tumor metastasis. Pathological and immunohistochemical staining results further showed that the lung tissue metastasis was significantly increased in mice of acetaminophen group. qRT-PCR results showed that mRNA expressions of barrier related proteins such as Claudin 5, Occludin, ZO-1, and DSG2 were significantly decreased in lung tissues of mice in acetaminophen group. Conclusion Acetaminophen may reduce the expression of epithelial barrier-related proteins, induce epithelial barrier dysfunction, and then induce the risk of tumor metastasis.

R965.1

天津市自然科学基金资助项目（18JCZDJC99300）