Effects Of Propofol On LPS-Induced Brain Injury In Rats

Objective:To investigate the effects of propofol on LPS-induced brain injury in rats and the possible mechanism.Methods:Seventy-two Sprague-Dawley rats of both sexes, aged6weeks, weighing200～250g, were randomly divided into3groups (n=24each):control group (group C)、LPS group (group L)、propofol group (group P). Brain injury was produced by injection of LPS1mg/kg via the left internal carotid artery in L and P groups. Propofol100mg/kg was injected intraperitoneally immediately after the LPS administration in group P, while the equal volume of normal saline was given instead of propofol in group L, the equal volume of normal saline was given instead of LPS and propofol in group C. Six rats in each group were sacrificed at6、24、48and72h after intraperitoneal administration. The brains tissues were immediately removed for the determination of water content, the expression of HMGB1and phosphorylation of p38MAPK by western blot, the expression of NF-KBp65and iNOS by immunohistochemistry. Pathological change in brain was observed with light microscope.Results:The brain water content was significantly increased, the expression of HMGB1、p38MAPK、NF-κBp65and iNOS was up-regulated in group L as compared to group C. The expression levels of HMGB1、 p38MAPK、NF-κBp65and iNOS protein in group L increased at6h after LPS administration, reached the peak at24h, and still higher than those of group C at48h and72h(P<0.05). The brain water content and expression of HMGB1、p38MAPK、NF-κBp65and iNOS were significantly lower in group P than in group L (P<0.05). The microscopic examination showed that brain injury was attenuated in group P compared with group L.Conclusion:(1) LPS can induce brain injury, which may be correlated with upregulation the expression of HMGB1and iNOS, activated p38MAPK and NF-κB signal pathway may involved in the development process;(2) Propofol can reduce the LPS-induced brain injury, which may be related with downregulation the expression of HMGB1and iNOS, inactivated p38MAPK and NF-κB signal pathway, thereby reduced the inflammatory response.