Isosteviol Sodium Inhibits Astrogliosis after Cerebral Ischemia/Reperfusion Injury in Rats.
Isosteviol Sodium Inhibits Astrogliosis after Cerebral Ischemia/Reperfusion Injury in Rats.
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DOI：
10.1248/bpb.b17-00921
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发表时间：
2018-04
影响因子：
2
通讯作者：
Hao Zhang;Xiaoou Sun;Yanxiang Xie;Fang Tian;Hui Hu;Wen Tan
中科院分区：
文献类型：
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作者：
Hao Zhang;Xiaoou Sun;Yanxiang Xie;Fang Tian;Hui Hu;Wen Tan
以往的研究表明，异甜菊醇钠（STVNa）对大鼠急性局灶性脑缺血具有神经保护作用，但其确切的作用机制和理想的治疗方案尚不清楚。为了寻找一种合理的STVNa给药方法，并确定其可能的治疗机制，我们表征了单剂量和多剂量STVNa在大鼠脑缺血/再灌注（I/R）损伤中的保护作用。损伤后腹腔内给予10 mg/kg STVNa单次和多次治疗，以研究其神经保护作用。缺血7 d后评估神经行为缺陷和梗死体积。两种STVNa治疗均减少梗死体积，改善神经行为，保护细胞形态，增强神经元存活，并抑制细胞凋亡。多次治疗效果优于单次治疗。反应性星形胶质细胞增生在损伤后7 d明显，多次STVNa治疗可显著抑制，但单次治疗无效。这些结果表明STVNa在I/R的急性期和延迟期通过不同的机制发挥神经保护作用。具体地，发现STVNa在损伤的延迟阶段中的神经保护伴随着星形胶质细胞增生的抑制。
Previous reports have indicated that isosteviol sodium (STVNa) has neuroprotective effects against acute focal cerebral ischemia in rats; however, the exact underlying mechanisms and ideal treatment paradigm are not known. To find a reasonable method for STVNa administration and to determine its possible therapeutic mechanisms, we characterized the protective effects of single-dose and multiple-dose STVNa in cerebral ischemic/reperfusion (I/R) injury in rats. Single and multiple treatments with 10 mg/kg STVNa were administered intraperitoneally after injury to investigate its neuroprotective effects. Neurobehavioral deficits and infarct volume were assessed 7 d after ischemia. Both STVNa treatments reduced infarct volumes, improved neurological behaviors, preserved cellular morphology, enhanced neuronal survival, and suppressed cell apoptosis. Multiple treatments performed better than single treatment. Reactive astrogliosis was apparent at 7 d after injury and was significantly inhibited by multiple STVNa treatments but not single treatment. These results indicate that STVNa exerts neuroprotection by different mechanisms in the acute and delayed phases of I/R. Specifically, STVNa neuroprotection in the delayed phase of injury was found to be accompanied with the inhibition of astrogliosis.