吡格列酮对大鼠脑缺血再灌注的保护作用

The Protective Effects of Pioglitazon on Rats with Focal Cerebral Ischemia-reperfusion Injury

目的观察吡格列酮(PGZ)在局灶脑缺血再灌注模型大鼠中对核因子(NF-κB)、基质金属蛋白酶-9(MMP-9)表达的影响,探讨PGZ在本过程中对细胞外基质的破坏是否发挥抑制作用。方法将60只健康雄性大鼠平均分为5个实验组(n=12):正常对照组、模型组/缺血再灌注组和PGZ低剂量组10 mg·kg^(-1)、PGZ中剂量组15 mg·kg^(-1)、PGZ高剂量组20 mg·kg^(-1)),相应处理后,予行为学评分,得到的标本组织通过免疫组化、蛋白质印迹法分析大鼠海马组织中NF-κB、MMP-9的表达差异。结果模型组大鼠与正常对照组比较神经功能学评分及NF-κB和MMP-9的表达均升高(P<0.01);PGZ各剂量组神经功能学评分及NF-κB、MMP-9表达较模型组降低(P<0.01),不同PGZ剂量组间有显著差异(P<0.05)。结论本实验表明PGZ可以抑制NF-κB、MMP-9的表达抑制细胞外基质破坏起到减轻脑缺血再灌注损伤的作用,从而发挥其脑保护功能。

Objective To observe the effects of PGZ on the expression of NF-κB, MMP-9 with focal cerebral ischemia-reperfu-sion and explore whether there’ s the inhibiting effect of PGZ for the damage of extracellular matrix. Methods 60 healthy rats are e-venly divided into 5 groups （n=12）：the normal control group, the modal/ischemia-reperfusion group, the low dose of PGZ （10 mg ·kg-1 ） group, the middle dose of PGZ （15 mg·kg-1 ） group and the high dose of PGZ （20 mg·kg-1 ） group. After the correspond-ing processing, expressive difference of NF-κB and MMP-9 in Hippocampal tissue of rats can be analyzed by immune-histochemical and the western blot. Results Compared the model set with the normal control group, the neurological scores and the expression of NF-κB and MMP-9 of the ischemia-reperfusion group are increased （P〈0. 01）. The neurological scores and the expression of NF-κB and MMP-9 of the three different level dose PGZ groups are decreased in contrast to those of the ischemia-reperfusion group （ P〈0. 01）. The differences are obvious among the three different level dose PGZ groups. Conclusion The experiment indicates that PGZ can resist the damage of extracellular matrix through restraining the expression of NF-κB and MMP-9, alleviate the cerebral ischemia-reperfusion injury and play the role of brain protection.