Protective Effects Of Astaxanthin On Brain In Septic Rats

Objective To study the protective effects of Astaxanthin(AST)on brain in sepsis rats,and explore possible mechanism.Methods 48 healthy SD male rats were randomly assigned to sham,sepsis,AST-treated and vehicle-treated groups,according to different observation time point,each group was further assigned to two subgroups at 12 h and 24 h.The rats that did not survive to the observation time point were eliminated,the number of rats was supplemented to ensure that there were six surviving rats in each subgroups.As previously described,cecal ligation and puncture(CLP)was used in sepsis,AST-treated and vehicle-treated groups to establish sepsis model,the sham group only underwent an identical laparotomy but without CLP.All rats were injected subcutaneously with saline(3ml / 100g)for fluid resuscitation,the astaxanthin group was treated with gavage astaxanthin(50mg / kg),the vehicle group was treated with gavage equal volume DMSO within10 minutes after successful modeling.Samples of blood and brain tissue were collected at 12 h and24h in each subgroup.Serum TNF-?,IL-6,NF-?B,NSE and S100 B protein were detected by ELISA.Brain tissue MDA levels and SOD activities were detected by colorimetric method.The wet and dry weights of left brain tissue were weighed and calculated their water content.The right brain tissues were fixed with formaldehyde and stained with HE,and observing pathological changes under a microscope.Results(1)There were no significant differences of Serum inflammation markers(TNF-?,IL-6,NF-?B),serum brain injury markers(S100B protein,NSE),brain tissue oxidative stress injury markers(MDA,SOD activity)and brain water content in the sham group at 12 h and 24h(P> 0.05).Compared with the sham group,the SOD activity in the sepsis group was significantly reduced(P <0.05),the rest of indicators were increased.Among them,NF-?B was significantly increased at 24 hours,and the other indicators were significantly increased in all phases(P <0.05).Compared with the CLP group,astaxanthin treatment can reduce serum inflammation markers,brain injury markers,oxidative stress markers and brain water content,and restore SODactivity.Among them,TNF-?,IL-6,NSE,S100 B,and MDA were significantly reduced in each phase(P <0.05);NF-?B was significantly reduced at 24h(P <0.05),but no statistical difference at12h(P> 0.05);SOD activity recovered significantly at 12h(P <0.05),but no statistical difference at 24h(P> 0.05);brain water content decreased significantly at 12 h and no significant change at24 h.(2)In the sham group,the structure of brain tissue was clear,nerve cells were complete,abundant Nissl body can be seen in the neurons' cells.The nerve fibers were uniformly stained,pale pink,neatly arranged,with clear texture and no infiltration of inflammatory cells;Compared with the sham group,the CLP group nerve fibers were disordered,the structure was loose,the number of neuron cells was significantly reduced at the same magnification,the neuron cell body was condensed,and the staining is deeper,the Nissl body were significantly reduced or disappeared,and the surrounding inflammatory cells infiltrated obviously;Astaxanthin treatment can reduce pathological changes of brain tissue.The nerve fiber structure was slightly loose,but there was no obvious disorder in arrangement structure,the Nissl body were seen in the neurons,and the inflammatory cell infiltration was reduced.(3)All the indexes of vehicle-treated group changed consistently with those in the sepsis group,and there was no significant difference between them(P> 0.05),indicating that the vehicle had no significant effect on this experimental study.Conclusion Astaxanthin has a protective effect on the brain of sepsis rats,and the mechanism may be related to astaxanthin inhibition of inflammatory response and reduction of oxidative stress injury.