Habib Samar, Hany Heba, Elzoheiry Manal, Elmehankar Manar S, Elgendy Suzan H, Hussin Emadeldeen, Elmasry Khaled, Aboukamar Wafaa A
Department of Medical Parasitology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Acta Parasitol. 2025 Jun 2;70(3):120. doi: 10.1007/s11686-025-01028-9.
The autophagy process is critical for cell survival, homeostasis, and functions. Autophagy deregulation was linked to several liver diseases; however, little is known about autophagy status during schistosomiasis and praziquantel (PZQ) treatment. This study is exploring autophagy status during schistosomiasis and praziquantel treatment in the hepatocytes, macrophages, and hepatic stellate cells (HSCs) in mice, and linking the variations in these levels to the parasitic parameters.
CD-1 Swiss female albino mice were allocated into three groups: negative control, Schistosoma mansoni (S. mansoni)-infected, and the third group was S. mansoni-infected and treated with PZQ. Liver sections were stained for autophagy markers (LC3 and P62) by immunohistochemistry.
At 12 weeks post infection, P62 increased in S. mansoni-infected mice in hepatocytes, macrophages, and HSCs compared to negative controls (P = 0.038, P < 0.001, P = 0.004, respectively) and decreased in PZQ-treated group compared to S. mansoni-infected mice in hepatocytes and macrophages only (P < 0.001, P = 0.004, respectively). LC3 displayed higher levels in S. mansoni-infected mice compared to negative controls in hepatocytes, macrophages, and HSCs (P = 0.01, P < 0.001, P < 0.001, respectively), while in PZQ-treated group, it decreased in macrophages and HSCs compared to S. mansoni-infected mice (P = 0.016, P < 0.001, respectively). Correlations were found between the number of eggs and autophagy status, mostly in HSCs.
Schistosomiasis inhibits autophagy in hepatocytes, macrophages, and HSCs, while PZQ treatment reverses autophagy levels in hepatocytes and macrophages, but not in HSCs. More research is needed to understand the autophagy behavior in HSCs during different stages of schistosomiasis to promote development of autophagy-based anti-fibrotic drugs.
自噬过程对细胞存活、内环境稳定及功能至关重要。自噬失调与多种肝脏疾病相关；然而，对于血吸虫病及吡喹酮（PZQ）治疗期间的自噬状态知之甚少。本研究旨在探究小鼠肝细胞、巨噬细胞及肝星状细胞（HSCs）在血吸虫病及吡喹酮治疗期间的自噬状态，并将这些水平的变化与寄生虫参数联系起来。
将CD-1瑞士雌性白化小鼠分为三组：阴性对照组、曼氏血吸虫（S. mansoni）感染组，第三组为曼氏血吸虫感染并用吡喹酮治疗组。通过免疫组织化学对肝切片进行自噬标志物（LC3和P62）染色。
感染后12周，与阴性对照组相比，曼氏血吸虫感染小鼠的肝细胞、巨噬细胞及肝星状细胞中P62增加（分别为P = 0.038、P < 0.001、P = 0.004），而与曼氏血吸虫感染小鼠相比，吡喹酮治疗组仅在肝细胞和巨噬细胞中P62减少（分别为P < 0.001、P = 0.004）。与阴性对照组相比，曼氏血吸虫感染小鼠的肝细胞、巨噬细胞及肝星状细胞中LC3水平更高（分别为P = 0.01、P < 0.001、P < 0.001），而在吡喹酮治疗组中，与曼氏血吸虫感染小鼠相比，巨噬细胞和肝星状细胞中的LC3减少（分别为P = 0.016、P < 0.001）。发现虫卵数量与自噬状态之间存在相关性，主要在肝星状细胞中。
血吸虫病抑制肝细胞、巨噬细胞及肝星状细胞中的自噬，而吡喹酮治疗可逆转肝细胞和巨噬细胞中的自噬水平，但不能逆转肝星状细胞中的自噬水平。需要更多研究来了解血吸虫病不同阶段肝星状细胞中的自噬行为，以促进基于自噬的抗纤维化药物的开发。
