The protective function of peroxisome proliferator-activated receptor gamma agonist to focal cerebral ischemia-reperfusion injury in mice model
10.3760/cma.j.issn.1006-7876.2009.03.013
- VernacularTitle:过氧化物酶体增殖物激活受体γ激动剂对小鼠局灶性脑缺血再灌注损伤的保护作用
- Author:
Jinlin SHANG
;
Li SUN
;
Hao LIANG
;
Yan CHENG
- Publication Type:Journal Article
- Keywords:
Brain ischemia;
Reperfusion injury;
PPAR gamma
- From:
Chinese Journal of Neurology
2009;42(3):190-194
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate neuroprotective function of peroxisome proliferator-activated receptor gamma (PPARγ) agonist, rosiglitazone against reperfusion injury after focal cerebral ischemia in mice model.Methods To establish cerebral isebemia-reperfusion injury mice model, adult male mice underwent 2 hours of middle cerebral artery occlusion followed by 22 hours reperfusion (MCAO/R). One hour before MCAO/R, mice were treated with either vehicle (MCAO/R group) or rosiglitazone (6 mg/kg, rosiglitazone group). 2,3,5-triphenyhetrazolium chloride (TIC) staining was applied to determine the volume of cerebralinfarction.TheneurologicaldeficitwasscoredatZeaLonga 5-pointscale. Myeloperoxidase (MPO) activity was measured in brain tissue as an index of neutrophil accumulation. RT-PCR, immunohistochemistry and Western blot were performed to examine the mRNA and protein expression of pro-inflammatory mediators (ICAM-1, IL-1β and COX-2).Results (1) The volume of cerebral infarction in rosiglitazone group was significantly decreased from that of MCAO/R group ( 29. 1 ± 6. 6 vs 57.8 ± 9. 7 ,t = 5. 980, P < 0. 01 ), and rosiglitazone markedly improved neurological function in treated mice than MCAO/R mice(1.2 +0.4 vs 3.3 ±0.8, t =5.812, P<0.01). (2) Compared with MCAO/R group, MPO activity in the rosiglitazone-treated group was significantly lower ((0. 049 + 0. 005 ) U/g vs (0. 083 ±0. 008) U/g,t =5. 904, P <0. 01 ). (3) The mRNA and protein expression of pro-inflammatory mediators (ICAM-1, IL-1β and COX-2) in rosiglitazone group were also significantly decreased from those in MCAO/R group, as demonstrated by RT-PCR (0.313 ±0.024, 0.205 ±0.007, 0.359 ±0.060, t = 7.464, 19.656, 29.319, P <0.01, respectively) and Western blot (0.274±0.014, 0.205±0.025, 0. 146±0.015, t=79.909, 21.392, 95. 105, P<0.01, respectively). ConclusionThe present study suggests that PPARγ agonist, rosiglitazone, has neureprotective properties to cerebral ischemia-reperfusian injury and that the protection is partially mediated via anti-inflarmmatory actions.