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Inhibition of ACE activity contributes to the intestinal structural compensation in a massive intestinal resection rat model

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Abstract

Background

Intestinal adaptation in short bowel syndrome (SBS) consists of increased epithelial cells (ECs) proliferation as well as apoptosis. Angiotensin-converting enzyme (ACE) has been shown to regulate ECs apoptosis. In this study, we investigated the effect of ACE inhibition on intestinal adaptation after small bowel resection (SBR) in a rat model.

Methods

Sprague–Dawley rats were used and were divided into four groups: (1) Sham group received an ileum transection (n = 6); (2) Sham + ACE-I group received an ileum transaction and lavage with ACE inhibitor (ACE-I, enalaprilat, 2 mg/kg/day) (n = 6); (3) SBS group received a 70 % mid-intestinal resection (n = 6); (4) SBS + ACE-I group received a 70 % mid-intestinal resection and lavage with enalaprilat (2 mg/kg/day) (n = 6). Sampling was done 10 days after surgery. ECs apoptosis was studied by TUNEL staining. ACE, angiotensin II (ANGII) receptor type 1 (AT1R) and receptor type 2 (AT2R) expressions were detected with RT-PCR and immunofluorescent confocal microscopy.

Results

SBR leads to significant intestinal hypertrophy. The addition of ACE-I to SBS rat resulted in a significant decline in ECs apoptosis. ACE mRNA expression was significantly elevated after SBS creation (0.24 ± 0.07 vs. 0.42 ± 0.11), and ACE-I administration further increased mucosal ACE mRNA expression (0.54 ± 0.12). Interestingly, AT1R mRNA expression showed a significant decline in the SBS group compared to Sham levels, and ACE-I administration increased AT1R mRNA expression to Sham levels. No significant difference in AT2R mRNA expression was found between Sham and SBS group.

Conclusion

These results offer further insight into the role of ACE on intestinal mucosal remolding after massive bowel resection. ACE-I may be beneficial to SBS patients via a reduction of the apoptotic rate, thus facilitating the degree of adaptation.

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Acknowledgments

This research was supported by the National Natural Science Foundation of China (NSFC 30973113, NSFC 30872465, NSFC 81020108023), the Scientific Research Foundation of The Third Military Medical University for the Returned Overseas Chinese Scholars and Chongqing Science and Technology Commission (CSTC2008BA5006).

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Correspondence to Hua Yang.

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Wang, W., Xiao, W., Sun, L. et al. Inhibition of ACE activity contributes to the intestinal structural compensation in a massive intestinal resection rat model. Pediatr Surg Int 28, 533–541 (2012). https://doi.org/10.1007/s00383-012-3075-9

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