目的 考察對乙酰氨基酚對Lewis肺癌荷瘤小鼠上皮屏障功能的影響，為臨床合理用藥提供參考。方法 C57BL/6小鼠的右腋處皮下接種2×10⁶個Lewis肺癌細胞，通過小鼠一般狀態(tài)和肺組織表面轉移灶考察對乙酰氨基酚對腫瘤肺轉移的影響。利用病理組織形態(tài)、HE染色、免疫組化等方法檢測腫瘤轉移情況，同時采用qRT-PCR法檢測屏障相關蛋白Claudin 5、Occludin、ZO-1、DSG2 mRNA表達水平，探討對乙酰氨基酚影響上皮屏障的潛在機制。結果 與對照組和模型組比較，大體形態(tài)觀察對乙酰氨基酚組小鼠肺組織出現(xiàn)了明顯的腫瘤轉移灶，病理及免疫組織化學染色結果進一步顯示對乙酰氨基酚組肺組織轉移灶明顯增加，qRT-PCR結果顯示對乙酰氨基酚組小鼠肺組織Claudin 5、Occludin、ZO-1、以及DSG2等屏障相關蛋白mRNA表達均顯著降低。結論 對乙酰氨基酚可以影響上皮屏障相關蛋白表達誘導上皮屏障功能障礙，并可能繼而有利于腫瘤轉移。

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

天津市自然科學基金資助項目（18JCZDJC99300）