Propofol alleviates intestinal ischemia/reperfusion injury in rats through p38 MAPK/NF-κB signaling pathway

L. Li, F. Shu, X.-Q. Wang, F. Wang, L. Cai, X. Zhao, H.-G. Lv

Department of Anaesthesiology, Honghui Hospital, Xi’an Jiaotong University, Xi’an, China. doctorlhg@163.com

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• Pharmacology

OBJECTIVE: The aim of this study was to investigate the influences of propofol on intestinal ischemia/reperfusion (I/R) injury in rats through the p38 mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-κB) signaling pathway.

MATERIALS AND METHODS: The models of intestinal I/R injury were first successfully established. All rats were randomly divided into 4 groups, namely, S group, I/R group, P group and P + S group. Pathological-morphological changes, injury score and wet-to-dry weight ratio of intestinal tissues as well as oxidative stress indexes in each group of rats were detected. Enzyme-linked immunosorbent assay (ELISA) was applied to measure the levels of inflammatory factors such as creatine kinase-MB (CK-MB), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in each group of rats. Furthermore, Western blotting (WB) assay was applied to determine the protein expression levels of p38 MAPK and NF-κB in different groups.

RESULTS: Intestinal tissue injury was the severest in I/R group, with the infiltration of massive inflammatory cells and oozing of blood (Figure 1A, I/R). Compared with those in I/R group, the infiltration of inflammatory cells and damage to intestinal villi were notably relieved in P group and P + S group, revealing that the intestinal mucosal injury was remarkably repaired in P group and P + S group (Figure 1A, P). Moreover, the intestinal tissue injury score was evidently higher in I/R group, P group and P + S group than that in S group (p<0.05). However, it was markedly lower in P group and P + S group than that in I/R group (p<0.05). I/R group, P group and P + S group exhibited significantly increased wet-to-dry weight ratio of intestinal tissues in comparison with S group (p<0.05). However, P group and P + S group exhibited distinctly lower wet-to-dry weight ratio of intestinal tissues than I/R group (p<0.05). The content of malondialdehyde (MDA) was reduced prominently, while that of superoxide dismutase (SOD) was elevated significantly in P group and P + S group in contrast with those in I/R group (p<0.05). On the contrary, P + S group displayed remarkably lower MDA content and higher SOD content than P group (p<0.05). The levels of CK-MB, TNF-α and IL-6 in the blood rose markedly in I/R group compared with those in S group (p<0.05). However, they declined evidently in P group and P + S group in contrast with those in I/R group (p<0.05). Besides, the protein expression level of phosphorylated p38 MAPK was significantly higher in I/R group, P group and P + S group than that in S group (p<0.05). However, no significant difference was observed in the protein expression of total p38 MAPK among the four groups (p>0.05). However, the protein expression level of phosphorylated p38 MAPK was distinctly down-regulated in P group and P + S group in comparison with that in I/R group (p<0.05). Finally, I/R group, P group and P + S group had a prominently higher protein expression level of NF-κB than S group (p<0.05). However, P group and P + S group exerted a significantly lower protein expression level of NF-κB than I/R group (p<0.05).

CONCLUSIONS: Propofol decreases the release of inflammatory factors and alleviates intestinal edema by inhibiting the p38 MAPK/NF-κB signaling pathway, thereby mitigating and treating the intestinal I/R injury in rats.

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