<sup>68</sup>Ga-FAPI Small Animal PET/CT in Rats with Peritoneal Fibrosis and the Therapeutic Effect of Sodium Butyrate
Peritoneal fibrosis (PF) is a common complication in peritoneal dialysis patients with end-stage renal disease. This study established a rat model of PF, used <sup>68</sup>Ga-FAPI PET/CT imaging to visualize PF, and evaluated the therapeutic effects and mechanism of action of sodium butyrate. The rat model of PF (<i>n</i> = 20) was induced by hyperglycemic peritoneal dialysate combined with lipopolysaccharide, the control group (<i>n</i> = 20) was given the same amount of normal saline, and the intervention group (<i>n</i> = 20) was given sodium butyrate by intraperitoneal injection. At 2, 4, 6, and 8 weeks, a peritoneal equilibration test was performed, and peritoneal tissues were collected for histological staining. Three rats from each group were randomly selected for <sup>68</sup>Ga-FAPI small animal PET/CT imaging. Compared with control rats, model group rats presented a decreased ultrafiltration volume, increased maximum glucose transport (<i>P</i> < 0.05), increased peritoneal thickness and fibrosis area, and upregulated α-SMA, COL I, TGF-β1, Smad3, and p-Smad3 expression in peritoneal tissues (<i>P</i> < 0.05) in a time-dependent manner. The sodium butyrate group improved peritoneal transport function (<i>P</i> < 0.05), alleviated collagen deposition, and downregulated α-SMA, COL I, TGF-β1, Smad3, and p-Smad3 while increasing Smad7 expression in peritoneal tissues (<i>P</i> < 0.05). <sup>68</sup>Ga uptake was markedly increased in the model group (<i>P</i> < 0.05) but was reduced after sodium butyrate treatment (<i>P</i> < 0.05). The SUVmax was positively correlated with peritoneal thickness; maximum glucose transport; and α-SMA, COL I, and FAP-α expression (<i>r</i> = 0.871, 0.845, 0.843, 0.659, 0.926) but negatively correlated with ultrafiltration volume (<i>r</i>= -0.894). In summary, <sup>68</sup>Ga-FAPI PET/CT could be a promising noninvasive approach for assessing peritoneal fibrosis that is superior to and safer than peritoneal biopsy. Sodium butyrate may attenuate peritoneal fibrosis by regulating the TGF-β1/Smad3 signaling pathway.
Authors
- Santao Ou (ORCID: https://orcid.org/0000-0003-4149-1996)
- Zhanwen Huang
- Yuexi Huang
- Mengxia Cao
- Jingyi Chen (ORCID: https://orcid.org/0000-0002-6011-5630)
- Yan Li (ORCID: https://orcid.org/0000-0002-6857-9464)
- Chunmei Guo
- Weihua Wu (ORCID: https://orcid.org/0000-0002-5824-7781)
- Zibei Wan
Institutions
- Affiliated Hospital of Southwest Medical University (CN)
- The People's Hospital of Guangxi Zhuang Autonomous Region (CN)
- The First People's Hospital of Guangyuan
Publication Details
- Journal
- Molecular Pharmaceutics
- Published
- 2025-02-12
- DOI
- https://doi.org/10.1021/acs.molpharmaceut.4c00998
- Citations
- 2
- Primary Topic
- Peptidase Inhibition and Analysis
- Type
- article
- Field-Weighted Citation Impact
- 2.09
Funders
- Department of Science and Technology of Sichuan Province
- Luzhou Science and Technology Bureau