Glucagon-like peptide-2 protects impaired intestinal mucosal barriers in obstructive jaundice rats

Abstract

Aim: To observe the protective effect of glucagon-like peptide-2 (GLP-2) on the intestinal barrier of rats with obstructive jaundice and determine the possible mechanisms of action involved in the protective effect.

Methods: Thirty-six Sprague-Dawley rats were randomly divided into a sham operation group, an obstructive jaundice group, and a GLP-2 group; each group consisted of 12 rats. The GLP-2 group was treated with GLP-2 after the day of surgery, whereas the other two groups were treated with the same concentration of normal saline. Alanine aminotransferase (ALT), total bilirubin, and endotoxin levels were recorded at 1, 3, 7, 10 and 14 d. Furthermore, on the 14(th) day, body weight, the wet weight of the small intestine, pathological changes of the small intestine and the immunoglobulin A (IgA) expressed by plasma cells located in the small intestinal lamina propria were recorded for each group.

Results: In the rat model, jaundice was obvious, and the rats' activity decreased 4-6 d post bile duct ligation. Compared with the sham operation group, the obstructive jaundice group displayed increased yellow staining of abdominal visceral serosa, decreased small intestine wet weight, thinning of the intestinal muscle layer and villi, villous atrophy, uneven height, fusion, partial villous epithelial cell shedding, substantial inflammatory cell infiltration and significantly reduced IgA expression. However, no significant gross changes were noted between the GLP-2 and sham groups. With time, the levels of ALT, endotoxin and bilirubin in the GLP-2 group were significantly increased compared with the sham group (P < 0.01). The increasing levels of the aforementioned markers were more significant in the obstructive jaundice group than in the GLP-2 group (P < 0.01).

Conclusion: GLP-2 reduces intestinal mucosal injuries in obstructive jaundice rats, which might be attributed to increased intestinal IgA and reduced bilirubin and endotoxin.

Keywords: Glucagon-like peptide-2; Intestinal mucosal barrier; Obstructive jaundice.

Figure 1

Glucagon-like peptide-2 protects impaired intestinal mucosa on day 14. A: Mesentery anatomy of the three groups; B: Body weights of the rats in three groups on day 14; C: Wet intestinal weights of the rats in the three groups on day 14. ^aP < 0.05 vs control, ^cP < 0.05, ^dP < 0.01, OB vs OBGLP-2;. C: Control; OB: Obstructive jaundice; OBGLP-2: Obstructive jaundice with GLP-2.

Figure 2

Intestinal mucosal pathological alterations as assessed by HE staining and sIgA immunohistochemical appearance on day 14. C: Control; OB: Obstructive jaundice; OBGLP-2: Obstructive jaundice with GLP-2.

Figure 3

Comparison of serum alanine aminotransferase (A), total bilirubin (B) and endotoxin levels (C) in three groups (n = 12). ^aP < 0.05, ^bP < 0.01, OB vs OBGLP-2. C: Control; OB: Obstructive jaundice; OBGLP-2: Obstructive jaundice with GLP-2.