Inhibition of p38 MAP kinase corrects biochemical and neurological deficits in experimental diabetic neuropathy
Inhibition of p38 MAP kinase corrects biochemical and neurological deficits in experimental diabetic neuropathy
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DOI：
10.1111/j.1749-6632.2002.tb04665.x
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发表时间：
2002-01-01
期刊：
影响因子：
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通讯作者：
Tomlinson, DR
中科院分区：
文献类型：
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作者：
Agthong, S;Tomlinson, DR
已知糖尿病激活大鼠和患者感觉神经元中的MAP激酶p38。在体外，葡萄糖和氧化应激联合激活感觉神经元中的p38，导致细胞损伤或死亡。因此，我们测试的假设，抑制MAP激酶p38可能会防止实验性糖尿病大鼠的神经功能障碍，如经典的神经传导减慢的缺陷。因此，用p38抑制剂SB 239063治疗链脲佐菌素糖尿病大鼠12周糖尿病方案的后半部分选择性地防止感觉神经元中的神经传导缺陷。这暗示MAP激酶p38的激活是实验性糖尿病神经病变功能障碍信号通路的早期步骤。
Diabetes is known to activate MAP kinase p38 in sensory neurons in both rats and patients. In vitro, activation of p38 in sensory neurons by combined glucose and oxidant stress causes cell damage or death. Consequently we tested the hypothesis that inhibition of MAP kinase p38 might prevent neuronal dysfunction in rats with experimental diabetes, such as the classical defect of slowed nerve conduction. Thus, treatment of streptozotocin-diabetic rats with the p38 inhibitor SB239063 for the second half of a 12-week diabetes protocol selectively prevented the nerve conduction deficit in sensory neurons. This implicates activation of MAP kinase p38 as an early step in the signal pathway to dysfunction in experimental diabetic neuropathy.