芍药苷对中动脉阻塞模型大鼠环氧酶通路表达的影响

Effect of paeoniflorin on cyclooxygense pathway in rats with middle cerebral artery occlusion

目的探讨芍药苷对大鼠大脑中动脉阻塞(MCAO)诱导的环氧酶代谢通路表达的影响。方法 120只雄性SD大鼠,随机分为假手术组、模型组、芍药苷低、中、高(10、20、40 mg/kg)剂量组、尼莫地平组。线栓法制作大鼠大脑中动脉缺血90 min,再灌注24 h模型。观察芍药苷对神经症状、梗死体积及脑含水量的影响,采用免疫组化SP法检测COX-2的表达情况,ELISA法测缺血侧额区皮质肿瘤坏死因子-α(TNF-α)、白介素1-β(IL-1β)、血栓素A2(TXA2)和前列腺素I2(PGI2)水平。结果芍药苷处理组较模型组能显著改善大鼠神经缺损症状,缩小梗死体积,降低缺血侧脑含水量,抑制COX-2阳性表达,减少TNF-α、IL-1β、TXA2的释放,提高PGI2水平。结论芍药苷可能通过抑制花生四烯酸的环氧酶代谢通路产生脑神经保护作用。

AIM To investigate effects of paeoniflorin on cyclooxygense pathways in rats with middle cerebral artery occlusion. METHODS One hundred and twenty male SD rats were randomly divided into six groups： sham operation group, cerebral ischemia-reperfusion model group, low, middle and high （10, 20 and 40 mg/kg） doses of paeoniflorin groups and Nimodipine group. The right middle cerebral artery of the rat was occluded by in- serting a thread through internal carotid artery for 90 rain and then reperfused for 24 h. The effects of paeoniflorin on neurological function scores, the infarction volume and brain water content were estimated. The expression of COX-2 in hippocampal CA1 was determined by immunohistochemistry and the contents of TNF-α, IL-1β, PGI2 and TXAEin frontal cortex of ischemic hemispheres were measured by ELISA method. RESULTS Compared with the model group, different doses of paeoniflorin significantly improved neurological scores and reduced the infarction volume and brain water content. In addition, paeoniflorin could inhibit COX-2＇ s expression and the release of TNF-α, IL-1β and TXAEand prevent the down-regulation of PGI2 induced by I/R injury. CONCLUSION The neuroprotective effects of paeoniflorin against focal cerebral ischemia-reperfusion rats may be attributed to inhibiting arachidonic acid expression via cyclooxygense pathways.