| Brain edema is one of the major pathologic change,It includs celluar edema and vascular edema. The mechanisms of infectious brain edema are very complex, many causes are involed.Cytokins are basic meditors of immunity. They have immense functions in the process of brain edema. And they involed the inflammatory cells activation and infiltration.The functions of cytokins are mostly complex in vivo, affect each other in their induction, regulation of receptor, and exertion of bioactivity.So an abound and sophisticated cytokin network was formed. Some studies have demonstrated that chemokins are expressed during the inflammation of centrol nervous system. Macrophage inflammatory protein 2(MIP-2) is the major member of ELR+CXC chemokins, which is produced by many cells. It's major biological function is to chemotaxe and active polymorphonuclear neutrophils (PMN). And there are complex realationship in MIP-2, interleukin 18(IL-18), interleukin 6(IL-6), interleukin 10(IL-10)and et al.They can affect each other. By injecting lioposacchride (LPS) into rat's caroid in this exprement, the model of brain edema was made. On the basis of brain edema, the change of MIP-2, IL-6, IL-10, IL-18 are monitored. Their functions and realations are explored by interfering of naloxone. The experiment will helps us understand pathogenesis of LPS inducing rat brain edema, provide new measures of theraphy.METHODS 84 healty adult SD rats that weight was from 180g to 200g, mailor femail, were randomly divided into three groups: normal saline group(NS group, n=28), 0.2ml normal saline was injected by carotid for each rat;LPS group(LPS group, n=28), The rat was applied 200ug LPS;Naloxone interfering group(NAL group, n=28), 1mg/kg naloxone was intraperitoneally injected at 10min, 1h, 2h, 6h, 12h and 2h before decapitation following LPS injection. Each group was divided into four groups: 4h,6h,12h, 24h. And each group had 7 rats. Rats were decapitated at different time point, and brain tissue samples were prepared. The content of water, even blue(EB), MIP-2, IL-18, IL-6,IL-10 in brain tissue was detected at different time point.RESULTS (l)Histopathological change:In LPS group.it could be found that the vascular and the space among vasculars began broaden, inflammatory cells infitrated. Gliocyte became tumefied, neurocyte became tumefied and was degenerated.In NAL group,brain cells began less tumefacient, pathological change became attenuated. (2)Brain water content and EB content:brain water content and EB content in NS group were relatively stable and had no significant difference in each point(p>0. 05). In LPS group, brain water content and EB content increased after LPS was injected 4h, and elevated maximally at 6h. Campared with NS group, brain water content and EB content were higher in LPS group at each time point. The difference was significant (p<0. 01).In NAL group, brain water content and EB content were lower compared with LPS group(p 0. 01), but higher than NS group(P<0.01). (3) Brain MIP-2 content: In LPS group, MIP-2 content increased after LPS was injected 4h, and elevated maximally at 12h. Compared with NS group, the content of MIP-2 in LPS group was higher, and the difference was significant(p<0.01). In NAL group, the content of MIP-2 was lower than LPS group(P<0.05 or p<0.01), but higher than NS group (P<0. 01). (4) Brain IL-18 content: In LPS group, IL-18 content increased after LPS was injected 4h, and elevated maximally at 6h and maintained higher levels at 12h. Compared with NS group, the difference was significant(p<0.01). In NAL group, the content of IL-18 was higher than NS group(/X0. 01), but lower than LPS group at time point of 4h, 6h, 12h(/X0. 05 or /X0.01), at time point of 24h, there was no significant difference (/D>0. 05). (5) Brain IL-6 content: In LPS group, IL-6 content increased after LPS was injected 4h, and elevated maximally at 6h. Compared with NS group, the content of IL~6 in LPS group was higher, and the difference was significant (/X0. 01). In NAL group, the content of IL-6 was lower than LPS group(/X0. 05 or p^0. 01), but higher than NS group (p<0. 01). (6) Brain IL-10 content: In LPS group, IL-10 content increased after LPS was injected 4h, and elevated maximally at 12h. Compared with NS group, the content of IL-10 in LPS group was higher,and the difference was significant(/X0. 01). In NAL group, the content of IL-10 was lower than LPS group but there was no significant difference, and higher than NS group(/X0. 01). (7)Relative relationship analysis among brain water content, EB content, IL-6 content, IL-10 content, IL-18 content, MIP-2 content in LPS group: Brain water content and EB content had positive relationship ( 7^0.743,/X0.01 ) .IL-18 content and water content had positive relationship (7=0.616, /X0. 01) .IL-18 content and EB content had positive relationship (t*=0. 497, /X0. 01) . IL-18 content and IL-6 content had positive relationship (t=0. 484, /X0. 01) . IL-18 content and MIP-2 content had positive relationship (t=0. 631, /X0. 01) ; IL-6 content and water content had positive relationship (t=0. 459, /X0. 05) .IL-6 content and EB content had positive relationship (t=0. 568, /X0. 05) ; IL-10 content and water content had positive relationship (7^0. 467, /X0. 05) . IL-10 content and IL-18 content had positive relationshipCT^O. 660, /X0. 01). IL-10 content and MIP-2 content had positive relationship (t-0. 619,/XO. 01) .CONCLUSIONS (l)By injecting LPS into rats' caroid,the animal model of infectious brain edema could be established, companied with increasing brain water and destroyed blood-brain barrier. Histopathological changeswere vascular and cytotoxic brain edema. (2) After injecting LPS into rats' caroid, the expression of MIP-2, IL-18, IL-6, IL-10 were increased, they could probably result in the increasing of brain water content and permeability of BBB. (3) IL-18 expressed earlier, and maintained higher levels longer. That could be speculated that IL-18 was important in inflammatory reactions. IL-18 content had positive relationship with MIP-2 content and IL-6 content. That could be speculated that IL-18 may induce the expression of MIP-2 and IL-6. (4) IL-10 content had positive relationship with IL-18 content and MIP-2 content. That could be speculated that IL-10 may had relationship with some inflammatory cytokins. (5) Naloxone could attenuate brain edema through inhibiting the expression of MIP-2, IL-18,IL-6 when it applied earlier and repeatedly. But no result on the expression of IL-10. |
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