Ye Xiao-Li, Lu Ling-Qun, Li Wei, Lou Qi, Guo Hong-Gang, Shi Qiao-Juan
Department of Pharmacy, The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, P.R. China.
Experimental Animal Center, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang 310013, P.R. China.
Exp Ther Med. 2017 May;13(5):1725-1734. doi: 10.3892/etm.2017.4197. Epub 2017 Mar 8.
Ampelopsin (AMP) is isolated from the Chinese medicinal herb (Hand-Mazz) and has been associated with numerous biological and pharmacological activities. However, it is not clear whether AMP has a direct protective effect on cerebral ischemia reperfusion injury. Therefore, the present study investigated its role in acute brain injury following focal cerebral ischemia in rats. The current study induced transient focal cerebral ischemia by performing middle cerebral artery occlusion (MCAO) for 60 min, followed by 24 h of reperfusion. Rats were exposed to 40, 80 and 160 mg/kg AMP by oral administration 30 min prior to MCAO and the cysteinyl leukotriene receptor 1-antagonist, pranlukast (0.1 mg/kg, i.p.) was used as a positive control. Neurological deficit scores were observed and an inclined board test was used to assess behavioral dysfunction. The coronal slices were stained with 3,5-triphenyltetrazolium chloride to determine the infarct volume and brain edema. Neuronal morphology was assessed in brain sections stained with cresyl violet and degenerating neurons were identified using Fluoro-Jade B staining. Blood-brain barrier permeability was determined with immunoglobulin (Ig)G immunohistochemistry. Interleukin (IL)-1β, tumor necrosis factor-α (TNF-α) in serum and cerebrospinal fluid were measured using ELISA kits. AMP at 80 and 160 mg/kg attenuated neurological deficits, reduced infarct volume, brain edema, IgG exudation and neuron degeneration and loss. Similar to pranlukast, AMP also inhibited the MCAO-induced IL-1β and TNF-α release. Thus, AMP has a neuroprotective effect on acute brain injury following focal cerebral ischemia in rats at an effective oral dose of 80-160 mg/kg. The results of the current study indicate a therapeutic role for AMP in the treatment of ischemic stroke.
白藜芦醇（AMP）是从中药材（毛叶蛇葡萄）中分离得到的，具有多种生物学和药理活性。然而，AMP对脑缺血再灌注损伤是否具有直接保护作用尚不清楚。因此，本研究探讨了其在大鼠局灶性脑缺血后急性脑损伤中的作用。本研究通过大脑中动脉闭塞（MCAO）60分钟，随后再灌注24小时诱导短暂性局灶性脑缺血。在MCAO前30分钟，大鼠经口给予40、80和160mg/kg的AMP，半胱氨酰白三烯受体1拮抗剂普仑司特（0.1mg/kg，腹腔注射）作为阳性对照。观察神经功能缺损评分，并采用倾斜板试验评估行为功能障碍。冠状切片用氯化三苯基四氮唑染色以确定梗死体积和脑水肿。用甲酚紫染色的脑切片评估神经元形态，并用Fluoro-Jade B染色鉴定变性神经元。用免疫球蛋白（Ig）G免疫组织化学法测定血脑屏障通透性。采用ELISA试剂盒测定血清和脑脊液中的白细胞介素（IL）-1β、肿瘤坏死因子-α（TNF-α）。80和160mg/kg的AMP减轻了神经功能缺损，减少了梗死体积、脑水肿、IgG渗出以及神经元变性和丢失。与普仑司特相似，AMP也抑制MCAO诱导IL-1β和TNF-α的释放。因此，AMP在有效口服剂量为80-160mg/kg时，对大鼠局灶性脑缺血后的急性脑损伤具有神经保护作用。本研究结果表明AMP在缺血性中风治疗中具有治疗作用。
