College of Rehabilitation, Hebei United University, Tangshan, Hebei Province, China.
Affiliated Hospital of Hebei United University, Tangshan, Hebei Province, China.
Neural Regen Res. 2014 Apr 1;9(7):749-56. doi: 10.4103/1673-5374.131581.
Activation of extracellular signal-regulated kinase 1/2 has been demonstrated in acute brain ischemia. We hypothesized that activated extracellular signal-regulated kinase 1/2 can protect hippocampal neurons from injury in a diabetic model after cerebral ischemia/reperfusion. In this study, transient whole-brain ischemia was induced by four-vessel occlusion in normal and diabetic rats, and extracellular signal-regulated kinase 1/2 inhibitor (U0126) was administered into diabetic rats 30 minutes before ischemia as a pretreatment. Results showed that the number of surviving neurons in the hippocampal CA1 region was reduced, extracellular signal-regulated kinase 1/2 phosphorylation and Ku70 activity were decreased, and pro-apoptotic Bax expression was upregulated after intervention using U0126. These findings demonstrate that inhibition of extracellular signal-regulated kinase 1/2 activity aggravated neuronal loss in the hippocampus in a diabetic rat after cerebral ischemia/reperfusion, further decreased DNA repairing ability and accelerated apoptosis in hippocampal neurons. Extracellular signal-regulated kinase 1/2 activation plays a neuroprotective role in hippocampal neurons in a diabetic rat after cerebral ischemia/reperfusion.
细胞外信号调节激酶 1/2 的激活已在急性脑缺血中得到证实。我们假设，在脑缺血/再灌注后的糖尿病模型中，激活的细胞外信号调节激酶 1/2 可以保护海马神经元免受损伤。在这项研究中，通过四血管闭塞在正常和糖尿病大鼠中诱导短暂性全脑缺血，并在缺血前 30 分钟向糖尿病大鼠给予细胞外信号调节激酶 1/2 抑制剂（U0126）作为预处理。结果表明，使用 U0126 干预后，海马 CA1 区存活神经元数量减少，细胞外信号调节激酶 1/2 磷酸化和 Ku70 活性降低，促凋亡 Bax 表达上调。这些发现表明，细胞外信号调节激酶 1/2 活性的抑制加重了脑缺血/再灌注后糖尿病大鼠海马神经元的丢失，进一步降低了海马神经元的 DNA 修复能力并加速了细胞凋亡。细胞外信号调节激酶 1/2 的激活在脑缺血/再灌注后糖尿病大鼠的海马神经元中发挥神经保护作用。
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