Gao Xiaochan, Ma Chaoran, Wang Hongjun, Zhang Chunnuan, Huang Yong
School of Animal Science and Technology, Henan University of Science and Technology, Luoyang, 471003, China.
Chemosphere. 2023 Jun;325:138383. doi: 10.1016/j.chemosphere.2023.138383. Epub 2023 Mar 10.
The mass production and discharge of carbon nanotubes (CNTs) to the water environment are of great concern since they threaten the health of organisms in the aquatic ecosystem. CNTs induce multi-organ injuries in fish, but limited literature is available regarding the mechanisms involved. In the present study, juvenile common carp (Cyprinus carpio) were exposed to multi-walled carbon nanotubes (MWCNTs) (0.25 mg L and 2.5 mg L) for four weeks. MWCNTs caused dose-dependent alterations in the pathological morphology of liver tissues. Ultrastructural changes manifested as nuclear deformation, chromatin condensation, endoplasmic reticulum (ER) disorderly arrangement, mitochondria vacuolation, and mitochondrial membrane destruction. TUNEL analysis indicated that the apoptosis rate in hepatocytes markedly increased upon exposure to MWCNTs. Moreover, the apoptosis was confirmed by significant upregulation of mRNA levels of apoptosis-related genes (Bcl-2, XBP1, Bax, and caspase3) in MWCNTs-exposure groups, except for Bcl-2 expression which was not significantly changed in HSC groups (2.5 mg L MWCNTs). Furthermore, real-time PCR assay indicated the increased expression of ER stress (ERS) marker genes (GRP78, PERK, and eIF2α) in the exposure groups compared to the control groups, suggesting that the PERK/eIF2α signaling pathway involved in the injuries of the liver tissue. Overall, the results above indicate that MWCNTs induce ERS by activating the PERK/eIF2α pathway in the liver of common carp, and resulted in the initiation of apoptosis procedure.
碳纳米管（CNTs）大量生产并排放到水环境中备受关注，因为它们威胁着水生生态系统中生物的健康。碳纳米管会导致鱼类多器官损伤，但关于其中涉及的机制的文献有限。在本研究中，将幼年鲤鱼（Cyprinus carpio）暴露于多壁碳纳米管（MWCNTs）（0.25毫克/升和2.5毫克/升）中四周。多壁碳纳米管导致肝脏组织病理形态发生剂量依赖性改变。超微结构变化表现为核变形、染色质浓缩、内质网（ER）排列紊乱、线粒体空泡化和线粒体膜破坏。TUNEL分析表明，暴露于多壁碳纳米管后肝细胞凋亡率显著增加。此外，多壁碳纳米管暴露组中凋亡相关基因（Bcl-2、XBP1、Bax和caspase3）的mRNA水平显著上调证实了凋亡，除了在高剂量组（2.5毫克/升多壁碳纳米管）中Bcl-2表达没有显著变化。此外，实时PCR分析表明，与对照组相比，暴露组中内质网应激（ERS）标记基因（GRP78、PERK和eIF2α）的表达增加，表明PERK/eIF2α信号通路参与了肝脏组织损伤。总体而言，上述结果表明，多壁碳纳米管通过激活鲤鱼肝脏中的PERK/eIF2α途径诱导内质网应激，并导致凋亡程序启动。
