Dose-dependent protective effect of bisperoxovanadium against acute cerebral ischemia in a rat model of ischemia/reperfusion injury.
Dose-dependent protective effect of bisperoxovanadium against acute cerebral ischemia in a rat model of ischemia/reperfusion injury.
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双过氧钒对缺血/再灌注损伤大鼠模型急性脑缺血的剂量依赖性保护作用
DOI：
10.3390/ijms140612013
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发表时间：
2013-06-05
影响因子：
5.6
通讯作者：
Tian HL
中科院分区：
文献类型：
--
作者：
Guo JY;Ding J;Yuan F;Chen H;Chen SW;Tian HL
PTEN(第10号染色体上缺失的磷酸酶和张力蛋白同源物)是一种脂类和蛋白的双特异性磷酸酶。PTEN的缺失最初是在许多人类癌症中发现的。双过氧钒(BPV)对PTEN的抑制作用可减轻缺血性脑损伤后的神经损伤。本研究旨在探讨大鼠局灶性脑缺血再灌注损伤后给予BPV的最佳神经保护剂量。采用大脑中动脉结扎法制备局灶性脑I/R损伤模型。再灌注后即刻腹腔注射BPV 0.25、0.50、1.0 mg/kg，以生理盐水为载体对照。1.0 mg/kg的BPV对脑损伤的减轻作用最大。该剂量的BPV还显著阻断了大鼠半暗带皮质的细胞凋亡。这一有益作用与半暗带皮层Akt磷酸化水平的增加有关。这些结果表明，PTEN的药理抑制作用以剂量依赖的方式对抗I/R损伤，其保护作用可能是通过上调磷酸肌醇-3激酶/Akt促生存通路来实现的，为抗缺血性脑损伤提供了一种新的治疗策略。
PTEN (phosphatase and tensin homologue deleted on chromosome 10) is a dual-specificity lipid and protein phosphatase. The loss of PTEN was originally discovered in numerous human cancers. PTEN inhibition by bisperoxovanadium (bpV) reduces neurological damage after ischemic brain injury. The purpose of this study was to identify the optimal neuroprotective dose of bpV when administrated after focal ischemia/reperfusion (I/R) injury in rats. Focal I/R injury was induced using the middle cerebral artery occlusion method. bpV at doses of 0.25, 0.50 and 1.0 mg/kg were injected intraperitoneally just after reperfusion, with saline serving as a vehicle control. A maximal reduction in brain injury was observed with 1.0 mg/kg bpV. This dose of bpV also significantly blocked apoptosis in the penumbral cortex of rats. This beneficial effect was associated with the increasing levels of Akt phosphorylation in the penumbral cortex. These results demonstrate that the pharmacological inhibition of PTEN protects against I/R injury in a dose-dependent manner and the protective effect might be induced through upregulation of the phosphoinositide-3 kinase/Akt pro-survival pathway, suggesting a new therapeutic strategy to combat ischemic brain injury.
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影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
2.9
作者：
Choi, YC;Lee, JH;Lee, KS
通讯作者：
Lee, KS
影响因子：
3.7
作者：
Walker CL;Walker MJ;Liu NK;Risberg EC;Gao X;Chen J;Xu XM
通讯作者：
Xu XM
影响因子：
25
作者：
Liu, Kai;Lu, Yi;Lee, Jae K.;Samara, Ramsey;Willenberg, Rafer;Sears-Kraxberger, Ilse;Tedeschi, Andrea;Park, Kevin Kyungsuk;Jin, Duo;Cai, Bin;Xu, Bengang;Connolly, Lauren;Steward, Oswald;Zheng, Binhai;He, Zhigang
通讯作者：
He, Zhigang
影响因子：
6.1
作者：
Huang X;Zhang H;Yang J;Wu J;McMahon J;Lin Y;Cao Z;Gruenthal M;Huang Y
通讯作者：
Huang Y