Angiotensin Converting Enzyme Involves In The Regulation Of The Intestinal Epithelial Cell Apoptosis In A Massive Intestinal Resection Rat Model

Background: Short bowel syndrome is a clinical syndrome due to different causes reduced intestinal absorption area, mainly diarrhea and severe nutritional disorder. After massive small bowel resection (SBR), the residual intestine undergoes a series of adaptive processes resulting in a significant increase in intestinal absorptive surface area. In addition to an increase in functional absorption, adaptation also consists of an increase in villus length and crypt depth, and an increased number of microvilli. This compensatory role is to rehabilitate patients with short bowel syndrome in the foundation and guarantee for how to improve the adaptability of the remaining bowel compensation, including structural and functional compensation is the key to prevention of intestinal failure. This adaptation requires a remodeling of the crypt-villus complex and includes significant increases in both epithelial cell (EC) proliferation as well as EC apoptosis, and both of these two opposing processes participate in the remodeling of the intestinal mucosa. To promote intestinal epithelial cell proliferation and inhibit apoptosis is critical to promote the rehabilitation of patients undergoes SBR.Angiotensin converting enzyme (ACE) has been previously detected in the mucosal epithelium in human, rat, as well as mouse intestine. Because ACE has been shown to promote apoptosis in various tissues. SBS was associated with an increase ACE expression. ACE appears to be associated with an up-regulation of intestinal EC apoptosis. The inhibition of ACE can promote the mucosal adaptation after intestinal resection. In this study, we investigate the effects of ACEI (ACE inhibitor, enalaprilat) on the bowel adaptation in a massive intestinal resection rat model and the pathway by which ACE modulates EC apoptosis.Methods: Sprague-Dawley rat were used, and were divided into three groups: 1) Sham group, received a ileum transection (n=6); 2) SBS group, received a 75% mid-intestinal resection (n=6); 3) ACEI group, received a 75% mid-intestinal resection, and lavage with ACE inhibitor (ACEI, enalaprilat, 2mg?kg-1?d-1)(n=6). All rats were provided with ordinary rat chow ad libitum after surgery. Recording body weight changes in rats everyday. Sampling was done 10 days after resection. Measuring intestinal villus height, crypt depth and mucosal thickness of histological changes, TUNEL assay was used to detect EC apoptosis. ACE,angiotensin II (ANGII) receptor type 1 (AT1R),receptor type 2(AT2R) expression were detected with RT-PCR and immunofluorescent confocal microscopy.Results:1,After massive bowel resection,the body weight recovery in ACEI group is faster than that in SBS group [(7.51±2.28) % vs. (1.54±3.05)%, P﹤0.05], but both are lower than the control group [(18.79±2.53)%,P﹤0.01] 10 days after surgery.2,Massive bowel resection led to significant intestinal hypertrophy. There was an increase in both villus height and crypt depth (total height) in the SBS group. Total height was increased about 50% compared with the sham group [(778±30μm) vs. (502±40μm), P﹤0.01], and the SBS+ACEI group was about 14% higher than the SBS group[(870±29μm), P﹤0.05].3,Bowel resection led to an increase in intestinal EC apoptosis [(5.46±0.95)% vs. (1.01±0.49)%, P﹤0.05]. And the addition of ACEI to SBS rat resulted in a significant decline in EC apoptosis [(2.39±0.70)%, P﹤0.05].4,The expression of ACE mRNA was significantly elevated after SBS creation [(0.24±0.07)% vs. (0.42±0.11)%, (P﹤0.05)] and ACEI administration further increased mucosal ACE expression [(0.54±0.12)%, (P﹤0.05)].5,After massive bowel resection, AT1R expression showed a significant decline,but there is no significant difference in AT2R expression was found between untreated Sham and SBS groups. And ACEI administration increased both AT1R and AT2R expression to SBS levels significantly.Conclusion: These results offer further insight into the role of ACE on intestinal mucosal remolding after massive bowel resection. ANGII receptor may be of very importance for ACE in the modulation of intestinal adaptation.