<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.

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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

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article

68Ga-FAPI Small Animal PET/CT in Rats with Peritoneal Fibrosis and the Therapeutic Effect of Sodium Butyrate

Santao Ou, Zhanwen Huang, Yuexi Huang, Mengxia Cao et al.
2 citations
Molecular Pharmaceutics
Peptidase Inhibition and Analysis
2.09
article

68Ga-FAPI Small Animal PET/CT in Rats with Peritoneal Fibrosis and the Therapeutic Effect of Sodium Butyrate

Santao Ou, Zhanwen Huang, Yuexi Huang, Mengxia Cao, Jingyi Chen, Yan Li, Chunmei Guo, Weihua Wu, Zibei Wan
article en
2 citations

Abstract

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.

Molecular PharmaceuticsVol. 22(3)
Affiliated Hospital of Southwest Medical University (CN), The People's Hospital of Guangxi Zhuang Autonomous Region (CN), The First People's Hospital of Guangyuan
Department of Science and Technology of Sichuan Province, Luzhou Science and Technology Bureau
Zero hunger
Openalex Percentile: Top 14%
Peptidase Inhibition and Analysis
2.09
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