摘要
目的探讨过氧化小体增殖剂激活型受体γ(PPARγ)激活剂对缺血再灌注脑组织的保护作用及其炎性机制。方法健康雄性SD大鼠分为假手术组、生理盐水干预组、小剂量吡格列酮(PPARγ激活剂)干预组、大剂量吡格列酮干预组。吡格列酮干预组在中脑动脉闭塞(MCAO)前3 d分别给予吡咯列酮,每日一次灌胃给药。剂量分别是:小剂量组为10 mg/kg,大剂量组为15 mg/kg。生理盐水干预组仅给予等量生理盐水。假手术组亦给予等量生理盐水。以缺血后24h作为观察时间点,对各指标进行比较分析。氯化三苯基四氮唑(TTC)染色测定脑梗死体积,生化法测定髓过氧化物酶(MPO)活性。结果小剂量吡格列酮干预组的脑梗死体积[(147±14)mm3]及大剂量吡格列酮干预组脑梗死体积[(121±16)mm3]均较生理盐水干预组[(183±17)mm3]小;小剂量吡格列酮干预组的MPO[(0.148±0.027)U/g]及大剂量吡格列酮干预组MPO[(0.096±0.021)U/g]均比生理盐水干预组[(0.203±0.022)U/g]降低,并且上述指标均呈现出随吡格列酮剂量的增加而下调幅度增强的趋势(P<0.05)。结论PPARγ激活剂应用后,可以减少缺血再灌注脑组织梗死体积及中性粒细胞的浸润。本研究提示调控炎性损伤路径可能是利用PPARγ激活剂对PPARγ这一靶点进行干预从而发挥抗脑缺血损伤的机制之一。
Objective To study the effects of peroxisome prolifterator-activated receptor gamma （PPARγ） agonist against the injury of ischemia-reperfusion brain tissue and the inflammation mechanisms. Methods Adult male SD rats were randomly divided into four groups ： sham-operation ＋ normal saline （ NS）, ischemia-reperfusion （I/R） ＋ NS, I/R ＋ low-dose Pioglitazone （ PGZ, PPARγ agonists, 10 mg/kg, once daily）, and I/R ＋ high-dose PGZ （15 mg/kg, once daily）. The volume of cerebral infraction was measured by TTC staining and the activities of Myeloperoxidase （MPO） were measured by biochemistrical methods at 24 hrs of ischemia. Results The cerebral infarction volume of the low-dose PGZ group （ 147 ± 14 mm^3 ） and the high-dose PGZ group （ 121 ± 16 mm^3 ） were significantly smaller than that of the I/R ＋ NS group （ 183 ± 17 mm^3 ） （P 〈 0.05 ）. The MPO activities of the low-dose PGZ group （0. 148 ± 0. 027 U/g） and the high-dose PGZ group （0.096±0. 021 U/g） were significantly reduced compared with that of the I/R ＋ NS group （0.203 ± 0.022 U/g） （P 〈 0.05 ）. The decreased infarction volume and MPO activities were associated with the dosage of PGZ. Conclusions PPARγ agonists may reduce the volume of cerebral infraction and the infiltrations of neutrophilic leukocytes. It provides the Drotective effects against I/R iniury possibly through regulating the inflammatory reaction.
出处
《国际神经病学神经外科学杂志》
2007年第2期121-124,共4页
Journal of International Neurology and Neurosurgery
基金
教育部博士点基金(0040533053)
湖南省卫生厅重点科研基金(a2004-002)
关键词
过氧化小体增殖剂激活型受体γ
脑缺血再灌注损伤
脑梗死体积
激活剂
吡格列酮
髓过氧化物酶
peroxisome prolifterator-activated receptor γ
cerebral ischemia-reperfusion injury
the volume of cerebral infarction
agonist
Pioglitazone
Myeloperoxidase
