Vasoactive intestinal peptide and methylprednisolone change intestinal Toll-like receptor mRNA expression in rats with endotoxic shock / 中国小儿急救医学

ABSTRACT

Objective To investigate the effect of vasoactive intestinal peptide (VIP) and methylprednisolone (MP) on Toll-like receptor (TLR)2/4 mRNA expression in endotoxin (lipopolysaccharide,LPS) induced shock.Methods Ninety Sprague-Dawley rats were randomly divided into LPS group (n =20),LPS + VIP group (n =20),LPS + MP group (n =20),LPS + VIP + MP group (n =20) and control group (n =10).LPS group injected intravenously LPS (E Coli O55B5) 10 mg/kg.LPS + VIP group,LPS + MP group and LPS + VIP + MP group were injected intravenously VIP 5 nmol/kg,MP 3 mg/kg and VIP 5 nmoL/kg + MP 3 mg/kg after LPS 10 mg/kg injection.The control group injected normal saline intravenously instead of LPS.The rats were sacrificed at 6 h and 24 h after injection and the intestine samples were collected.Pathological changes of the intestine were observed by microscopy.RT-PCR was used to detect the intestinal TLR2 mRNA and TLR4 mRNA expressions.Results Intestinal mucosa showed edema or necrotic change with structure of the microvilli disappeared after LPS injection.The inestinal lesions in VIP,MP and VIP + MP groups were milder than LPS group.At 6 h after LPS injection,TLR2 mRNA and TLR4 mRNA expressions were significantly up-regulated in LPS group,LPS + VIP group,LPS + MP group and LPS + VIP + MP group (TLR2 mRNA1.14 ±0.38,1.17 ±0.42,1.16 ±0.41,0.92 ± 0.29;TLR4 mRNA 1.21 ±0.18,1.04 ± 0.38,1.11 ± 0.34,1.01 ± 0.20) compared with the control group (0.32 ± 0.20,0.24 ± 0.17) (P ＜ 0.01).But there was no significant difference between LPS group,LPS + VIP group,LPS + MP group and LPS + VIP + MP group (P ＞ 0.05).At 24 h after LPS injection,TLR2 mRNA and TLR4 mRNA expressions in LPS + VIP group,LPS + MP group and LPS + VIP + MP group (TLR2 mRNA0.63 ± 0.12,0.59 ± 0.13,0.52 ±0.19;TLR4 mRNA 0.67 ±0.09,0.64 ±0.09,0.51 ±0.13) were significantly lower than LPS group (1.04 ± 0.38,0.82 ±0.18) (P ＜0.01) (P ＜0.05).Conclusion VIP and/or MP can mitigate intestinal injury induced by LPS shock.The gastrointestinal protection of VIP and glucocorticoids were related to downregulation signaling TLR2 mRNA and TLR4 mRNA expression.But VIP/MP and VIP + MP have no significant effect on expression of intestinal TLR2/4 mRNA until 24 h after LPS shock.