Abstract: OBJECTIVE 1.To explore the feasibility of PPAR-γ1 gene transfection via cerebral ventricle and the protective effect against cerebral ischemia reperfusion injury. 2.To observe if the effection against cerebral ischemia reperfusion injury is enhanced when transfecting of PPAR-γ1 gene via cerebral ventricle association with the Pioglitazone which is PPAR-γ’s agonist. METHODS 95 S-D rats were randomly divided into 6 groups.Each group was treated with corresponding agent via cerebral ventricle.In groupⅠand Ⅱwere injected by normal saline.In group Ⅲ,rat was injected with 0.1ml Adv- PPAR-γ1 and the group Ⅳ was Adv-EGFP. The group Ⅴ was intragastric administered with Pioglitazone. The group Ⅵ was administered with PPAR-γ1 via cerebral ventricle and intragastric administered with Pioglitazone at the same time. 3. After 3 days middle cerebral artery occlusion model was established.The groupⅠwas sham-operation group.In group Ⅱ-Ⅵ middle cerebral artery was obstructed for 90min and followed reperfusion for 24h. 4. 24 hours after operation sample was collected and cerebral infarction volume was measured by TTC staining, blood brain barrier permeability by Evan’s blue dye Perfusion,brain moisture capacity by W-D weight method. To observe the pathomorphology by light microscope and electron microscope. Measuring the activity of MPO. To observe the expression of IL-1β、ICAM-1、AQP-4 and MMP-9 protein by Western Blotting. RESULTS After transfecting Adv-EGFP plasmid,the fluorescence for EGFP was positive in brain tissue suggesting the successful transfection of virus gene.In response to I/R injury, cerebral infarction was occurred.Blood brain barrier permeability、brain moisture capacity、the activity of MPO were dramatically incresed and the expression of IL-1β、ICAM-1、AQP-4、MMP-9 protein were upregulated.After injected Adv-PPAR-γ1 via cerebral ventricle or intragastric administered with Pioglitazone could inhibited the above parameters of injured brain.The improvement by adv-PPAR-γ1 gene and Pioglitazone was enhanced by administration together. CONCLUSIONS 1.Transfection of PPAR-γ1 gene via cerebral ventricle was feasible and demostrated the protectiv effect against cerebral ischemia reperfusion injury. 2. Combined transefction of PPAR-γ1 gene and intragastric administration with Pioglitazone could enhance the protectiv effect against cerebral ischemia reperfusion injury. 3. The infiltrations of neutrophilic leukocytes could be reduced by PPAR-γ1 and the expreeion of IL-1β、ICAM-1、AQP-4、MMP-9 protein were downregulated.These results suggests that the protective effect of PPAR-γ1 on ischemia-reperfusion injury is through regulating the inflammatory reaction and apoptosis.
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