CGRP protects the intestinal barrier by reducing intestinal apoptosis in sepsis rats

Objective 　To investigate the mechanism of calcitonin gene-related peptide (CGRP) in protecting intestinal barrier integrity by reducing intestinal apoptosis in sepsis rats. Methods 　Thirty SD male rats were randomized into 5 groups (n=6): Normal group, sham group, sepsis group (CLP group), CGRP treatment group (CGRP group) and anti-CGRP group. Rats were injected with 0.5 ml CGRP (30 μg/kg) in the CGRP group and injected with 0.5 ml CGRP (30 μg/kg) and 0.5 ml CGRP8-37 (30 μg/kg) in the anti- CGRP group. Serum diamine oxidase (DAO) and D-lactic acid levels were measured 30 minutes before the operation and 48 hours after the modeling. Histopathological changes of the small intestine were observed by HE staining; apoptosis of small intestine was detected by TUNEL assay; the expression of phosphorylated Bcl-xl/Bcl-2 related death promoter (p-BAD), phosphorylated extracellular signal-regulated kinase (p-ERK), caspase-3 were observed by immunohistochemistry. Results 　Compared with the normal group, the small intestine tissues were significantly damaged in the CLP group, with increased apoptosis, decreased p-ERK and p-BAD expressions, increased caspase-3 expressions (P<0.05). Meanwhile, serum DAO and D-lactic acid levels significantly increased (P<0.05). The damage of the small intestine in the CGRP group was significantly reduced compared with the CLP group, with decreased apoptosis and caspase-3 expression, increased p-ERK and p-BAD expression and significantly decreased serum DAO and D-lactic acid levels (P<0.05). Compared with the CGRP group, the small intestine damage was significantly aggravated in the anti-CGRP group, with increased apoptosis, decreased p-ERK and p-BAD expressions, increased caspase-3 expressions, and significantly increased serum DAO and D-lactic acid levels (P<0.05). Conclusion 　Intestinal mucosal permeability and apoptosis increase in sepsis rats. CGRP protects the integrity of the intestinal mucosal barrier through reduced intestinal tissue apoptosis with increased p-ERK and p-BAD. DOI: 10.11855/j.issn.0577-7402.2019.12.06