论文部分内容阅读
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 investigate the protective effect and mechanism of peroxisome proliferator - activated receptor γ (PPARγ) on cerebral ischemia - reperfusion in rats. Methods Healthy male Sprague-Dawley rats were randomly divided into sham-operation group, saline intervention group, low-dose pioglitazone (PPARγ activator) intervention group and high-dose pioglitazone intervention group. Pioglitazone intervention group were given pioglitazone 3 days before middle cerebral artery occlusion (MCAO), once a day by intragastric administration. The doses were 10 mg / kg for the low-dose group and 15 mg / kg for the high-dose group. The saline intervention group was given only the same amount of normal saline. The sham operation group was also given the same amount of saline. 24h after ischemia as the observation time point, the indicators were compared. The volume of cerebral infarction was measured by TTC staining, and the activity of myeloperoxidase (MPO) was determined by biochemical method. Results The volume of cerebral infarction in small dose pioglitazone intervention group was (147 ± 14) mm3 and that in high dose pioglitazone intervention group (121 ± 16 mm3) was significantly lower than that in saline intervention group (183 ± 17 mm3) ; MPO [(0.148 ± 0.027) U / g] and MPO [(0.096 ± 0.021) U / g] in the low-dose pioglitazone intervention group were significantly higher than those in the saline intervention group (0.203 ± 0.022 U / g ] Decreased, and the above indicators showed a downward trend with the increasing dose of pioglitazone (P <0.05). Conclusion PPARγ activator can reduce infarct volume and neutrophil infiltration in cerebral ischemia-reperfusion rats. This study suggests that the regulation of inflammatory injury pathways may be one of the mechanisms by which PPARγ activator is used to interfere with the target of PPARγ to exert anti-ischemic damage.