To investigate the protective effect and specific mechanism of esmolol(ES) on sepsis-induced intestinal injury in rats.

Eighteen adult male SD rats were randomLy divided into three groups according to the random number table method: Sham group(6 rats), lipopolysaccharide(LPS) group(6 rats), and LPS+ ES group(6 rats). The sepsis-induced acute intestinal injury rat model was reproduced by intraperitoneal injection of lipopolysaccharide (LPS)(10 mg/kg). The Sham group only received an equivalent amount of saline. In LPS+ ES group, esmolol dilution (15 mg·kg^-1·h^-1) was continuously pumped through left internal jugular vein; normal saline was continuously pumped into Sham group and LPS group. The rats were sacrificed when the model was successfully constructed for 12 h. The blood samples and the small intestinal tissues were collected. The diamine oxidase (DAO) and intestinal fatty acid-binding protein(I-FABP) were examined by enzyme-linked immunosorbent assay(ELISA). The intestinal tissue injury was analyzed by HE staining. The concentration of (interleukin-6, IL-6) and (interleukin-10, IL-10) were measured by ELISA. The expression levels of Beclin-1, LC3-Ⅱ, and p-AMPK was detected by Western blotting.

Compared with Sham group, LPS group showed extensive vacuolization and inflammatory cell infiltration in submucosa and muscularis of small intestine, shortening of villi and blurring of structure under light microscope. After esmolol intervention, extensive vacuolization and inflammatory cell infiltration in submucosa and muscle layer were significantly reduced, villi became longer, and pathological damage was reduced. In LPS group, the levels of IL-6, IL-10, I-FABP and DAO were significantly higher than that of Sham group [(131.00±8.67)pg/mL vs (106.40±6.70)pg/mL; (116.62±9.09)pg/mL vs (103.23±7.38)pg/mL; (9.61±1.70)ng/mL vs (3.91±0.70)ng/mL; (234.30±30.14)ng/mL vs (37.49±12.11)ng/mL, respectively, all P<0.05]. The levels of IL-6, DAO, I-FABP in the LPS+ ES group were significantly decreased as compared with those in LPS group[(117.50±9.00)pg/mL vs 131.0±8.67)pg/mL; (5.34±1.10)pg/mL vs (9.61±1.70)pg/mL; (147.80±17.07)ng/mL vs (234.30±30.14)ng/mL, respectively, all P<0.05], but the expression of IL-10 was significantly increased in LPS+ ES group compared with that in LPS group [(129.74±10.94)pg/mL vs (116.62±9.09)pg/mL, P<0.05]. At the same time, compared with LPS group, the levels of Beclin-1, LC3-Ⅱ and p-AMPK was significantly decreased (all P<0.05), but the expression of Beclin-1, LC3-Ⅱ and p-AMPK protein was significantly higer in LPS+ ES group than those in LPS group(all P<0.05).

The protective effects of esmolol on sepsis-induced intestinal injury may be attributed to the up-regulation of AMPK-mediated autophagy and reduction of inflammatory response.