热带病与寄生虫学

热带病与寄生虫学 ›› 2026, Vol. 24 ›› Issue (1): 47-53.doi: 10.20199/j.issn.1672-2302.2026.01.009

• 实验研究 • 上一篇    下一篇

日本血吸虫慢性感染诱发小鼠肾脏纤维化的实验研究

胡婷婷1(), 赵成思2(), 林树晴1, 王桂芳1, 邱竞帆1, 张戎1, 刘新建1(), 王勇1()   

  1. 1 南京医科大学基础医学院， 江苏南京 211166
    2 南京大学医学院附属泰康仙林鼓楼医院
  • 收稿日期:2025-10-24 出版日期:2026-02-20 发布日期:2026-03-31
  • 通信作者: 刘新建，E-mail: liuxinjian@njmu.edu.cn；王勇，E-mail: yongwsh@njmu.edu.cn
  • 作者简介:胡婷婷，女，硕士在读，研究方向：感染与免疫。E-mail: httnjmu@stu.njmu.edu.cn;|赵成思，男，硕士，技师，研究方向：感染与免疫。E-mail: zcs1003678028@163.com
  • 基金资助:
    国家自然科学基金项目(82072301)

Experimental study on renal fibrosis induced by chronic Schistosoma japonicum infection in mouse models

HU Tingting1(), ZHAO Chengsi2(), LIN Shuqing1, WANG Guifang1, QIU Jingfan1, ZHANG Rong1, LIU Xinjian1(), WANG Yong1()   

  1. 1 School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, Jiangsu Province, China
    2 Taikang Xianlin Drum Tower Hospital Affiliated to Medical School, Nanjing University
  • Received:2025-10-24 Online:2026-02-20 Published:2026-03-31
  • Contact: LIU Xinjian, E-mail: liuxinjian@njmu.edu.cn; WANG Yong, E-mail: yongwsh@njmu.edu.cn

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摘要：

目的 探讨日本血吸虫慢性感染对小鼠肾脏纤维化的动态影响及其分子机制，为阐明血吸虫病肾病的发病机制提供实验依据。方法 建立C57BL/6J小鼠日本血吸虫慢性感染的模型（15只），同时设置未感染组（15只）。分别于感染后第12周、14周、16周收集小鼠肾脏组织（感染组和未感染组各5只）进行检测分析。采用qRT-PCR检测肾脏组织中纤维化标志物（α-SMA、CTGF、Col-1、Col-4）的mRNA表达水平，Western blot检测CTGF、Col-1、P-Smad2/3及Smad7的蛋白表达，免疫组织化学检测Smad7蛋白的表达丰度与细胞定位。使用日本血吸虫可溶性成虫抗原（soluble worm antigen, SWA）与转化生长因子-β（transforming growth factor-β, TGF-β）信号通路激活剂TGF-β1刺激体外培养的小鼠肾小球系膜细胞（MES-13），通过qRT-PCR检测纤维化标志物、Smad3和Smad7的mRNA表达水平，免疫荧光观察Col-1和α-SMA蛋白在细胞中的表达情况。结果 qRT-PCR结果显示，相较于未感染组，12周、14周、16周感染组小鼠肾脏组织α-SMA、CTGF、Col-1及Col-4 mRNA表达均上调（t=4.61、6.64、3.52，t=3.29、5.07、7.22，t=3.66、4.74、3.10，t=3.24、5.92、2.67；P均<0.05）。Western blot结果显示，相较于未感染组，各时间点感染组CTGF、Col-1蛋白表达均上调（t=4.07、7.39、8.84，t=3.08、4.21、4.85；P均<0.05）；14周感染组肾脏组织P-Smad2/3蛋白表达高于未感染组（t=3.61，P<0.05），Smad7蛋白表达低于未感染组（t=7.96，P<0.05）。体外实验表明，SWA与TGF-β1干预后，MES-13细胞α-SMA、CTGF、Col-1、Col-4及Smad3 mRNA表达均高于未干预组，Smad7 mRNA表达低于未干预组，3组mRNA表达差异有统计学意义（F=62.26、112.70、7.64、127.20、10.78、6.75，P均<0.05）；免疫荧光检测证实SWA组α-SMA与Col-1蛋白表达增强。结论 日本血吸虫慢性感染期小鼠肾脏存在持续纤维化状态，SWA直接激活TGF-β信号通路在纤维化致病中可能起到重要作用。

关键词: 日本血吸虫, 慢性感染, 可溶性成虫抗原, 肾脏纤维化, TGF-β1/Smad信号通路

Abstract:

Objective To investigate the dynamic effects of chronic Schistosoma japonicum infection on renal fibrosis in mice and its molecular mechanism, thereby providing experimental evidence for elucidating the pathogenesis of schistosomiasis-associated kidney injury. Methods A chronic Schistosoma japonicum infection model was established in C57BL/6J mice (n=15), and an uninfected group (n=15) was set up simultaneously. Kidney tissues were collected at 12, 14, and 16 weeks post-infection (n=5 per group: infected and uninfected control) for subsequent analysis. The mRNA expression levels of fibrosis markers (α-SMA, CTGF, Col-1, and Col-4) in kidney tissues were detected by quantitative real-time PCR (qRT-PCR), and protein expression of CTGF, Col-1, P-Smad2/3 and Smad7 was analyzed by Western blot. Smad7 protein expression abundance and cellular localization were assessed by immunohistochemistry. Mouse glomerular mesangial cells (MES-13) were stimulated in vitro with soluble adult worm antigen (SWA) and transforming growth factor-β (TGF-β) from Schistosoma japonicum. The mRNA expression levels of fibrosis markers, Smad3, and Smad7 were measured by qRT-PCR, and the expression of Col-1 and α-SMA proteins in cells was observed via immunofluorescence. Results qRT-PCR results showed that, compared with the uninfected group, the mRNA expression of α-SMA, CTGF, Col-1, and Col-4 in the kidneys of mice infected for 12, 14, and 16 weeks was significantly up-regulated (t=4.61, 6.64, 3.52; t=3.29, 5.07, 7.22; t=3.66, 4.74, 3.10; t=3.24, 5.92, 2.67, all P<0.05). Western blot analysis revealed that the protein expression levels of CTGF and Col-1 were markedly increased at all time points in the infected groups compared to the uninfected group (t=4.07, 7.39, 8.84; t=3.08, 4.21, 4.85, all P<0.05). The expression of P-Smad2/3 protein in kidney tissues of the 14-week infection group was higher than that in the uninfected group (t=3.61, P<0.05), whereas the expression of Smad7 protein was lower than that in the uninfected group (t=7.96, P<0.05). In vitro experiments showed that after the intervention of SWA and TGF-β1, the mRNA expressions of α-SMA, CTGF, Col-1, Col-4 and Smad3 in MES-13 cells were all higher than those in the non-intervention group, while the mRNA expression of Smad7 was lower than that in the non-intervention group, There were statistically significant differences in mRNA expression among the three groups (F=62.26, 112.70, 7.64, 127.20, 10.78, 6.75, all P<0.05). Immunofluorescence confirmed enhanced expression of α-SMA and Col-1 proteins in the SWA group. Conclusion Chronic Schistosoma japonicum infection induces a sustained state of renal fibrosis in mouse models. The direct activation of the TGF-β signaling pathway by SWA may play an important role in the pathogenesis of fibrosis.

Key words: Schistosoma japonicum, Chronic infection, Soluble worm antigen (SWA), Renal fibrosis, TGF-β/Smad signaling pathway

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