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吡喹酮治疗后日本血吸虫感染小鼠肝脏中Septin4的表达

Expression of Septin4 in Schistosoma japonicum-infected mouse livers after praziquantel treatment.

作者信息

Zhu Dandan, Song Ke, Chen Jinling, Wang Jianxin, Sun Xiaolei, Qian Hongyan, Gu Xijuan, Zhang Lingbo, Qin Yongwei, Duan Yinong

机构信息

Department of Pathogen Biology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong, 226001, Jiangsu, People's Republic of China.

Laboratory Medicine Center, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu, People's Republic of China.

出版信息

Parasit Vectors. 2015 Jan 13;8:19. doi: 10.1186/s13071-015-0640-9.

Abstract

BACKGROUND

Septin4 (SEPT4) exists widely in human tissues and is related to mechanical stability, actin dynamics, membrane trafficking, viral replication and apoptosis. Data from many studies have suggested that SEPT4 plays a significant role in liver fibrosis. SEPT4 is down-regulated in the model of CCl4 and BDL treated liver fibrosis. However, it is up-regulated and peaked at 12 weeks post-infection (p.i.), and then decreased subsequently in Schistosoma japonicum (S. japonicum) egg-induced liver fibrosis. The aim of this study was to observe the dynamic alteration of SEPT4 after the treatment of praziquantel (PZQ) in ICR mice infected with S. japonicum.

METHODS

Expression of SEPT4 was determined by western blot, immunofluorescence and qRT-PCR. And pro-inflammatory cytokines IL-6 and TNF-α were detected by qRT-PCR. The number of eggs, the diameter of egg granulomas and fibrosis-associated genes were also measured.

RESULTS

Our results showed that the granulomatous inflammation was reduced, whereafter the expression of SEPT4 on hepatic stellate cells (HSCs) was decreased after PZQ anti-schistosome therapy. And the variation tendency of SEPT4 had positive correlation with the inflammatory response in the area of S. japonicum egg granulomas.

CONCLUSIONS

Based on these findings, the inhibition of the expression of the SEPT4 by PZQ might be due to alleviation of the inflammatory response at the chronic and advanced stage of S. japonicum infection.

摘要

背景

Septin4(SEPT4)广泛存在于人体组织中,与机械稳定性、肌动蛋白动力学、膜运输、病毒复制及细胞凋亡相关。众多研究数据表明,SEPT4在肝纤维化中发挥重要作用。在四氯化碳和胆管结扎诱导的肝纤维化模型中,SEPT4表达下调。然而,在日本血吸虫卵诱导的肝纤维化中,SEPT4在感染后12周上调并达到峰值,随后下降。本研究旨在观察吡喹酮(PZQ)治疗日本血吸虫感染的ICR小鼠后SEPT4的动态变化。

方法

采用蛋白质免疫印迹法、免疫荧光法及实时定量逆转录聚合酶链反应(qRT-PCR)检测SEPT4的表达。通过qRT-PCR检测促炎细胞因子白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)。同时检测虫卵数量、虫卵肉芽肿直径及纤维化相关基因。

结果

结果显示,吡喹酮抗血吸虫治疗后,肉芽肿性炎症减轻,肝星状细胞(HSCs)上SEPT4的表达降低。SEPT4的变化趋势与日本血吸虫卵肉芽肿区域的炎症反应呈正相关。

结论

基于这些发现,吡喹酮抑制SEPT4的表达可能是由于减轻了日本血吸虫感染慢性晚期的炎症反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9ff/4298944/2b4e6854bfe8/13071_2015_640_Fig1_HTML.jpg

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