Puerarin protects against ischemic brain injury in a rat model of transient focal ischemia

Puerarin protects against ischemic brain injury in a rat model of transient focal ischemia
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葛根素可预防短暂性局部缺血大鼠模型中的缺血性脑损伤

DOI:
10.1179/174313209x444017
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发表时间:
2009-05-01
影响因子:
1.9
通讯作者:
Luo, Yumin
Luo, Yumin
中科院分区:
医学4区
文献类型:
--
作者:
Gao, Li;Ji, Xunming;Luo, Yumin

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摘要目标:本研究旨在探讨中药葛根素对脑缺血再灌注后缺血性脑损伤的保护作用及其可能的机制。研究方法:通过大脑中动脉闭塞2小时,然后再灌注长达72小时来诱导缺血/再灌注损伤的动物模型。将大鼠随机分为4组(n=6/组):葛根素100,200和400 mg/kg或生理盐水,腹腔内给药。再灌注72小时后,通过2%氯化三苯基四氮唑染色测定神经功能结局和梗死体积。采用末端脱氧核苷酸转移酶生物素-dUTP缺口末端标记法检测脑细胞损伤(n=5/组)。通过酶联免疫吸附试验检测促红细胞生成素活化(n=5/组)。结果如下:与溶剂生理盐水组相比,200 mg/kg(p=0.045)和400 mg/kg(p=0.0002)剂量的葛根素可减少梗死体积,但100 mg/kg(p=0.387)剂量时则无此作用。葛根素400 mg/kg(p=0.015)可改善神经功能结局,但100 mg/kg(p=0.68)或200 mg/kg(p=0.056)则无改善。再灌注后4、24和72 h,葛根素组与对照组相比,末端脱氧核苷酸转移酶生物素-dUTP缺口末端标记染色细胞数明显减少。葛根素治疗组的促红细胞生成素活性高于溶剂组。讨论内容:葛根素在200和400 mg/kg剂量下对大鼠具有神经保护作用,在短暂性大脑中动脉闭塞后腹膜内给药,这可能部分是由于促红细胞生成素活性的激活。
Abstract Objectives: This study examines the efficacy of puerarin, a drug used in traditional Chinese medicine, in attenuating ischemic brain injury after cerebral ischemia and reperfusion, and explores possible mechanisms underlying neuroprotective effects. Methods: The animal model of ischemia/reperfusion injury was induced by middle cerebral artery occlusion for 2 hours followed by up to 72 hour reperfusion. The rats were randomly assigned into four groups (n=6/group): puerarin at 100, 200 and 400 mg/kg or saline, administered intraperitoneally. Neurological outcome and infarct volume by 2% triphenyl tetrazolium chloride staining were determined 72 hours after reperfusion. Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling staining was used to detect the cell damage of brains (n=5/group). Erythropoietin activation was detected by enzyme-linked immunosorbent assay (n=5/group). Results: Compared with the vehicle saline group, puerarin decreased infarction volume at doses of 200 mg/kg (p=0.045) and 400 mg/kg (p=0.0002), but not at 100 mg/kg (p=0.387). Functional neurological outcome was improved with puerarin at 400 mg/kg (p=0.015), but not at 100 mg/kg (p=0.68) or 200 mg/kg (p=0.056). Puerarin significantly decreased the terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling staining cells compared with the vehicle group 4, 24 and 72 hours after reperfusion. The erythropoietin activity was higher in puerarin treated group compared with the vehicle group. Discussion: Puerarin has neuroprotection effects in rats at doses of 200 and 400 mg/kg, administered intraperitoneally after transient middle cerebral artery occlusion which may be partly due to activation of erythropoietin activity.