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目的:探讨蝙蝠葛酚性碱(phenolic alkaloids of Menispermum dauricum,PAMD)对脑缺血再灌注大鼠的神经保护作用及其机制。方法:大鼠局灶性脑缺血模型采用大脑中动脉线栓法制作。动物随机分为假手术组,缺血再灌注组,PAMD低(25 mg·kg~(-1))、中(50 mg·kg~(-1))、高(75 mg·kg~(-1))剂量治疗组。持续栓塞2 h拔出线栓,再灌注4 h,然后断头取脑。干湿重法求出脑组织含水量,伊文思蓝含量测定法观察血脑屏障通透性。分离皮层组织,免疫印迹方法检测NR1和NR2A及各自对应的磷酸化蛋白。结果:(1)PAMD可以减少脑缺血再灌注大鼠脑组织含水量(P<0.05),降低脑缺血再灌注大鼠血脑屏障通透性(P<0.05);(2)与假手术组比较,缺血再灌注组NR1,NR2A,p-NR2A表达无明显变化,p-NR1表达减少(P<0.05);与缺血再灌注组比较,PAMD使p-NR1表达增多(P<0.05),NR2A表达减少(P<0.05)。结论:PAMD可通过调节p-NR1和NR2A对脑缺血再灌注大鼠发挥神经保护作用。
Aims: To investigate the neuroprotective effects of phenolic alkaloids of Menispermum dauricum (PAMD) on cerebral ischemia-reperfusion in rats and its mechanism. Methods: The model of focal cerebral ischemia in rats was made by middle cerebral artery occlusion method. The animals were randomly divided into sham operation group, ischemia reperfusion group, PAMD low (25 mg · kg -1), medium (50 mg · kg -1) and high (75 mg · kg -1) 1)) dose treatment group. Continuous embolization 2 h pull out the line bolt, reperfusion 4 h, and then decapitated brain. Dry-wet method to find the water content of brain tissue, Evans blue content determination of blood-brain barrier permeability. Cortical tissues were isolated and immunoblotted for the detection of NR1 and NR2A and their corresponding phosphorylated proteins. Results: (1) PAMD could reduce the water content of brain tissue in rats with cerebral ischemia-reperfusion (P <0.05) and decrease the permeability of blood-brain barrier in rats with cerebral ischemia / reperfusion (P <0.05) Compared with the ischemia-reperfusion group, the expression of p-NR1 was increased (P <0.01), and the expression of p-NR1 was decreased (P < 0.05), NR2A expression decreased (P <0.05). Conclusion: PAMD can exert neuroprotective effects on cerebral ischemia-reperfusion rats by regulating the expression of p-NR1 and NR2A.