Changes Of FKN And IL18 Expressing In Rats After Cerebral Ischemia-Reperfusion By Rosiglitazone Maleate

Background and objectiveit is very complex in the pathophysiology of Ischemia-reperfusion injury,.now the cytokine activation and leukocyte aggregation increase are thought to play a key role in it. Fractalkine (FKN) and interleukin-18 (IL-18), newly discovered proinflammatory cytokines, can mediate the upregulation of many inflammatory mediators, and promote leukocyte adhesion and aggregation.IL-18 is also able to activate NF-KB to induce FKN expression increased, which can cause inflammatory cascade and aggravate the degree of injure. Studies have found that IL-18 and FKN are closely related to the development of brain ischemia-reperfusion injury.Peroxisome proliferators activated receptor gamma, (PPARy) is a ligand-activated transcription factor, belonging to the nuclear receptor superfamily, which can inhibit the activation of NF-KB and expression of inflammatory cytokines, It plays a protective role in heart, brain, kidney, intestines and other vital organs of ischemia and reperfusion injury, but its mechanism is still not very clear.. This study will use 0.5,2,5 mg·kg-1 three different doses of PPARy ligand rosiglitazone (ROSI) for the intervention, with observing the FKN and IL-18 expression of focal cerebral ischemia and reperfusion penumbra, TTC staining to compare the size of infarction, combined with pathology and neurologic impairment,we study the Mechanism of the protective effect by ROSI in order to find a new way. for the treatment of cerebrovascular disease.MethodsThe healthy male sprague-dawley rats weighting 250～280g were randomly divided into five groups:sham operation group (n=12), NS control group (n=12), Rosiglitazone maleate 0.5,2 and 4 mg·kg-1 Three dose treatment group (n=36). Focal cerebral ischemia was induced by the intraluminal suture for middle cerebral artery occlusion. Rosiglitazone maleate 0.5,2 and 4 mg·kg-1 were taken orally immediately or 2 h after MCA occlusion, TTC staining was used to measure the infarct area.The pathologic changes were observed by hematoxylin and eosin (HE) staining.The protein expression of FKN,IL-18 were measured with methods of immunohistochemistry..Results1. Compared with I/R group, treatment with ROSI decrease the grade of the rat neurological defects except 0.5mg·kg-1 after reperfusion.2. Typical neural necrosis could be observed in I/R group and all TSG groups by HE staining after reperfusion.3. By TTC staining, the infarction area of 2,5mg·kg-1 large and medium dose group was significantly less than 0.5mg·kg-1 dose group and NS control group, and the former was no significant difference for the infarction area.4. FKN and IL-18 in the sham operation group were expressed little, and in the 2,5mg·kg-1 large and medium dose group it was significantly lower than brain 0.5mg·kg-1 dose in the intervention group and NS control group. ConclusionPPARy ligand rosiglitazone ameliorated brain ischemic injury after an 24 h MCA occlusion and inhibited the inflammatory response by decrease the expressing of FKN and IL-18 after an ischemia reperfusion in this study.