Department of Clinical Laboratory, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People's Republic of China.
Department of Endoscopy, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China.
Parasitol Res. 2024 Oct 23;123(10):359. doi: 10.1007/s00436-024-08382-z.
An in vivo mouse model of Clonorchis sinensis (C. sinensis) infection with or without the administration of autophagy inhibitor chloroquine (CQ) stimulation was established to assess the possible involvement of autophagic response during C. sinensis infection. Abnormal liver function was observed at 4, 6, and 8 weeks post-infection, as indicated by elevated levels of ALT/GPT, AST/GOT, TBIL, and α-SMA in the infected groups. These findings indicated that C. sinensis infection activated autophagy, as shown by a decreased LC3II/I ratio and accumulated P62 expression in infected mice. Interestingly, CQ administration exhibited dual and opposing effects during the infection. In the early stage of infection, the engagement of CQ appeared to mitigate symptoms by reducing inflammation and fibrotic responses. However, in the later stage of infection, CQ might contribute to parasite survival by evading autophagic targeting, thereby exacerbating hepatic impairment and worsening liver fibrosis. Autophagy in liver was suppressed throughout the infection. These observations attested that C. sinensis infection triggered autophagy, and highlighted a complex role for CQ, with both protective and detrimental effects, in the in vivo process of C. sinensis infection.
建立了伴有或不伴有自噬抑制剂氯喹（CQ）刺激的华支睾吸虫（C. sinensis）感染的体内小鼠模型，以评估自噬反应在华支睾吸虫感染过程中的可能参与。感染后 4、6 和 8 周观察到肝功能异常，感染组的 ALT/GPT、AST/GOT、TBIL 和 α-SMA 水平升高。这些发现表明华支睾吸虫感染激活了自噬，这表现为感染小鼠中 LC3II/I 比值降低和 P62 表达增加。有趣的是，CQ 给药在感染过程中表现出双重且相反的作用。在感染的早期阶段，CQ 的参与似乎通过减轻炎症和纤维化反应来减轻症状。然而，在感染的后期阶段，CQ 可能通过逃避自噬靶向来帮助寄生虫存活，从而加重肝损伤并加重肝纤维化。整个感染过程中肝内自噬受到抑制。这些观察结果证实华支睾吸虫感染触发了自噬，并强调了 CQ 在华支睾吸虫感染的体内过程中具有复杂的作用，既有保护作用也有损害作用。
