Humanin is a novel neuroprotective agent against stroke
Humanin is a novel neuroprotective agent against stroke
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DOI：
10.1161/01.str.0000242772.94277.1f
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发表时间：
2006-10-01
期刊：
影响因子：
8.3
通讯作者：
Chua, Balvin H. L.
中科院分区：
文献类型：
--
作者：
Xu, Xingshun;Chua, Chu C.;Chua, Balvin H. L.
背景和目的-Humanin (HN) 是一种 24 个氨基酸的肽，以其保护神经元免受阿尔茨海默病相关蛋白造成的损伤的能力而闻名。本研究探讨了 HNG（HN 的一种有效形式）对小鼠局灶性脑缺血/再灌注损伤的神经保护作用。方法-小鼠大脑中动脉闭塞 75 分钟，然后进行 24 小时再灌注。小鼠在缺血前30分钟用0.1μg HNG（脑室内）进行预处理；缺血后0、2、4和6小时给药；或在缺血前1小时用1μg HNG（腹膜内）预处理。评估神经功能缺损和脑梗塞体积。分别通过TUNEL和蛋白质印迹分析测量神经元凋亡和活化的聚（ADP-核糖）聚合酶表达。通过蛋白质印迹分析检查激活的ERK。结果-缺血前30分钟用0.1μg HNG（脑室内）预处理使脑梗塞体积从56.2+/-3.0%减少到26.1+/-1.4%（P<0.01）。再灌注 4 小时后进行 HNG 治疗后，脑梗塞体积减少至 45.6 +/- 2.6%（P < 0.05）。缺血前1小时或再灌注2小时后用1μg HNG（腹膜内）预处理，可显着减少脑梗塞体积。 HNG 还显着改善神经功能并抑制神经元凋亡以及聚（ADP-核糖）聚合酶激活。在用 HNG 治疗的小鼠中观察到磷酸-ERK 显着降低，而磷酸-JNK 和磷酸-p38 水平没有改变。结论 - 我们的结果表明 HNG 可以保护小鼠免受脑缺血/再灌注损伤。 HNG 至少部分通过抑制 ERK 激活来提供体内神经保护。这些发现表明 HNG 在治疗中风中具有潜在的治疗作用。
Background and Purpose-Humanin (HN) is a 24-amino acid peptide best known for its ability to protect neurons from damage caused by Alzheimer disease-related proteins. This study examines the neuroprotective effects of HNG (a potent form of HN) on focal cerebral ischemia/reperfusion injury in mice.Methods-Mice underwent middle cerebral artery occlusion for 75 minutes followed by 24-hour reperfusion. Mice were pretreated with 0.1 mu g HNG (intracerebroventricularly) 30 minutes before ischemia; posureated at 0, 2, 4, and 6 hours after ischemia; or pretreated with 1 mu g HNG (intraperitoneally) 1 hour before ischemia. Neurological deficits and cerebral infarct volume were evaluated. Neuronal apoptosis and activated poly(ADP-ribose) polymerase expression were measured by TUNEL and Western blot analysis, respectively. Activated ERKs were examined by Western blot analysis.Results-Pretreatment with 0.1 mu g HNG (intracerebroventricularly) 30 minutes before ischemia reduced cerebral infarct volume from 56.2 +/- 3.0% to 26.1 +/- 1.4% (P < 0.01). HNG posttreatment after 4 hours of reperfusion reduced cerebral infarct volume to 45.6 +/- 2.6% (P < 0.05). Pretreatment with 1 mu g HNG (intraperitoneally) 1 hour before ischemia or posttreatment after 2 hours of reperfusion reduced cerebral infarct volume significantly. HNG also significantly improved neurological function and inhibited both neuronal apoptosis as well as poly(ADP-ribose) polymerase activation. A significant decrease of phospho-ERK was observed in mice treated with HNG, whereas phospho-JNK and phospho-p38 levels were not altered.Conclusions-Our results demonstrate that HNG protects against cerebral ischemia/reperfusion injury in mice. HNG offers neuroprotection in vivo at least in part by inhibiting ERK activation. These findings suggest a potential therapeutic role for HNG in the treatment of stroke.