吡格列酮对脑缺血再灌注损害的保护作用及对血小板活化因子和P-选择素表达的影响

Effects of Pioglitazone on protection and expressions of platelet activating factor and P-selectin in brain ischemia reperfusion injury

目的研究吡格列酮对脑缺血再灌注损害的保护作用及对血小板活化因子(PAF)和P-选择素(Ps)表达的影响。方法用线栓法建立脑缺血再灌注大鼠模型。制模前7 d起,分别予以大剂量吡格列酮组大鼠20 mg/(kg.d)、小剂量吡格列酮组大鼠10 mg/(kg.d)吡格列酮灌胃,对照组大鼠给等量生理盐水灌胃,连续7 d。在缺血再灌注24 h后,给大鼠进行神经功能缺损评分,脑组织2,3,5-氯化三苯基四氮唑染色、苏木精-伊红染色,观察脑梗死体积、脑水肿程度及病理学变化。采用免疫组化法检测大鼠脑组织PAF和Ps的表达。结果与对照组比较,大剂量吡格列酮组和小剂量吡格列酮组的神经功能缺损评分显著降低、脑梗死体积显著缩小(P<0.05～0.01);病理改变明显较轻。大剂量吡格列酮组的脑水肿程度显著低于对照组(P<0.05),小剂量吡格列酮组与对照组脑水肿程度的差异无统计学意义。大剂量和小剂量吡格列酮组脑组织PAF阳性细胞数、Ps阳性血管数明显少于对照组,大剂量吡格列酮组的PAF阳性细胞数明显少于小剂量吡格列酮组(P<0.05～0.01)。结论吡格列酮预处理能减轻缺血再灌注脑损害,降低脑组织PAF和Ps的表达,其可能是通过减轻缺血再灌注后的炎症反应而起到脑保护作用。

Objective To evaluate the effects of Pioglitazone on protection and expressions of platelet activating factor （PAF） and P-selectin （Ps） in brain isehemia reperfusion injury. Methods The rat models of ischemia reperfusion were established by embolige middle cerebral artery occlusion. High dose Pioglitazone （HP） group and low dose Pioglitazone （LP） group were given Pioglitazone 20 mg/（ kg d） and 10 mg/（ kg d） respectively by gavage for 7 d before making model, control group was given equivalent volume of normal saline. At 24 h after the onset of reperfusion, the neurological deficit score was measured, and the infarct volume, brain edema and pathologic changes were observed by 2,3,5-triphenyltetrazolium chloride staining and hematoxylin-eosin staining. The expression of PAF and Ps was tested by immunohistochemistry. Results Compared with control group, the neurological deficit scores in HP and LP groups were significantly decreased, and the cerebral infarct volume were significantly smaller （P 〈 O. 05 -0.01 ） ; the pathological changes were significantly lighter. The degree of brain edema in HP group was significantly lower than that in the control group （P 〈 0. 05 ）. The difference of the degree of brain edema between LP group and control group was no statistical significance. The PAF positive cells and P-selectin positive vasulars of brain tissue in HP and LP groups were significantly less than those in the control group; and the PAF positive cells of brain tissue in HP groups was significantly less than that in the LP group （ P 〈 0. 05 - 0. 01 ）. Conclusions Pioglitazone preconditioning can reduce ischemia reperfusion brain damage, decrease the expression of PAF and Ps in brain tissue. Which make brain protection effects maybe by reducing the inflammatory response followed by the isehemic reperfusion injury.