Volume 21 Issue 6
Jun.  2023
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Article Navigation >  Chinese Journal of General Practice  > 2023  >  21(6): 927-931
CHEN Shoufeng, ZHANG Shuchao, LI Zhong, SUN Wei, LIU Beibei, YANG Xiaohuai, GUO Yuanyuan. The mechanism of rapamycin-induced autophagy to inhibit urethral fibrosis after injury in rats[J]. Chinese Journal of General Practice, 2023, 21(6): 927-931. doi: 10.16766/j.cnki.issn.1674-4152.003017
Citation: CHEN Shoufeng, ZHANG Shuchao, LI Zhong, SUN Wei, LIU Beibei, YANG Xiaohuai, GUO Yuanyuan. The mechanism of rapamycin-induced autophagy to inhibit urethral fibrosis after injury in rats[J]. Chinese Journal of General Practice, 2023, 21(6): 927-931. doi: 10.16766/j.cnki.issn.1674-4152.003017
shu

The mechanism of rapamycin-induced autophagy to inhibit urethral fibrosis after injury in rats

doi: 10.16766/j.cnki.issn.1674-4152.003017

  • Department of Urology, the First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, China

Funds:

 gxyqZD2019038

 KJ2021A0752

  • Received Date: 2022-08-13
    Available Online: 2023-08-26
    Abstract
  •   Objective  To investigate the effect and mechanism of rapamycin (Rapa) on the formation of urethral stricture and fibroblast in rats.  Methods  The rat (SD male rats, body weight 250-300 g) urethral stricture model was established and divided into negative control group, positive control group and Rapa+3-Methyladenine (3-MA) group by using the random nuber table method, with 10 rats in eah group. The urethral tissues of rats were collected at 14 d after operation, and the morphological changes of urethral tissues were observed by HE staining, and the changes of collagen were detected by Masson staining. The expression of α-SMA was observed by immunohistochemistry. HLF-1 cells were divided into control group, Rapa group and 3-MA+Rapa group. Transwell assay was applied to detect cell migration and invasion ability, flow cytometry to detect cell cycle and apoptosis, and Western blotting to detect LC3 expression.  Results  HE staining showed that urethral stricture degree of rats in the Rapa group was significantly reduced compared with that in the positive control group. Masson and immunohistochemical staining showed that collagen and α-SMA expression in the injured urethra tissues were increased in both the positive control group and Rapa group compared with that in the negative control group. However, the expressions of collagen and α-SMA in Rapa group were significantly lower than those in positive control group. Compared with the control group, the migration and invasion ability of HLF-1 cells in Rapa group were gradually decreased in a dose-dependent relationship (all P < 0.05), while the inhibition of Rapa on the migration, invasion ability of HLF-1 cells was decreased after the addition of 3-MA intervention (all P < 0.05). Flow cytometry and Western blotting results showed a significant increase in apoptosis in the Rapa group compared to the control group (all P < 0.05), and a dose-dependent increase in cellular LC3 expression (all P < 0.05).  Conclusion  Rapamycin can relieve the fibrosis after urethral tissue injury in rats, inhibit the migration and invasion of HLF-1 cells, and induce the apoptosis of HLF-1 cells, which may be achieved by inducing autophagy.

     

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