Protective effect of LPS preconditioning on intestinal mucosa in a rat mode of hemorrhagic shock

doi:10.3969/j.issn.1002-1949.2015.10.017

Abstract：Objective To investigate whether lipopolysaccharide preconditioning is able to relieve the intestinal injury caused by hemorrhagic shock in a rat mode .Methods Forty-two male Sprague-Daweley rats were divided into three groups randomly , namely Control , hemorrhagic shock (HS) and LPS precondioning (LPS+HS) group.The rats of Control group were only intubated , those of HS group were shed to a mean arterial pressure ( MAP) of 35-40 mmHg and maintained at this level for an hour and subsequently followed by resuscitation with 0.9% sodium chloride, and the animals of LPS+HS group were received an dose with of sterilized purified Escherichia coli LPS intraperitoneally (0.1 mg/kg) for five consecutive days prior to hemorrhagic shock challenge .The distal segments of ileum were harvested at 3 hour, 6 hour and 12 hour after resuscitation .Intestinal mucosal damage was assessed according to the grading of intestinal tissue injury by the document .The protein concentration of TNF-αin small intestinal tissue and in serum were detected by ELISA; protein levels of TLR4 were determined with Western blot .Results Preconditioning with sublethal LPS remarkably alleviated the injury of intestinal mucosa in rats when subjected to shock challenge .The animals received pretreatment with LPS showed a prominently reduced intestinal mucosal damage score and TNF -αconcentration in intestinal mucosa compared to saline -pretreated animals ( P<0.01 in 3 h, 6 h, 12 h time points, respectively ) .Although TLR4 was higher at 3 h group than Control group , it was lower significantly in LPS preconditioning rats than in saline preconditioning group .Moreover, the protein level of TLR4 at 6 h and 12 h group in LPS preconditioning rats were close to sham group .Conclusion These findings indicate that endotoxin tolerance by multiple exposure a low concentration of LPS has ability to alleviate intestinal mucosa injury in rats when received hemorrhagic shock .The mechanism may depend on decreased TLR4 expression within intestinal mucosa , which may ameliorate inflammatory response of intestinal mucosa .