Diabetic encephalopathy (DE) has been defined as one of the major complications of diabetes, characterized by neurochemical and neurodegenerative changes. However, the molecular mechanism of DE are not fully elucidated at present. Here, the primary hippocampal neurons were cultured in vitro with high glucose (HG) to induce diabetes-like effects, and mice were given streptozotocin (STZ) to induce a model of type 1 diabetes mellitus (T1D) mice. The administration of sulforaphane (SF) were used to observe the protective effects on the hippocampal neurons. We found that the expression of glucose-regulated protein 78 (GRP78), a typical endoplasmic reticulum chaperone, showed a trend of increasing in the early phase but decreasing in the late phase of both HG-induced primary hippocampal neurons and T1D mice. However, SF suppressed the apoptosis induced by HG in vitro and in vivo through TUNEL assay and caspase3 immunofluorescence staining. Meanwhile, the administration of SF suppressed the upregulation of CHOP, Bax and p-JNK protein and the downregulation of Bcl-2 protein induced by HG in hippocampal neurons in vitro and in vivo. The caspase12 gene was upregulated only at 4 weeks in T1D mice compared with control mice, and the upregulation was suppressed by SF. In addition, the combined administration of SF and PX12, which is an inhibitor of thioredoxin (Trx), eliminated the protective effects of SF. We conclude that HG induced the development of endoplasmic reticulum stress (ERS) in hippocampal neurons, eventually leading to the apoptosis of neurons. SF prevented the ERS and attenuates the hippocampal neuron apoptosis induced by HG both in vitro and in vivo. The underlying mechanism may be involved in the suppression of the CHOP-Bax/Bcl-2, JNK and caspase12 signaling pathways by SF through the Trx-1 target protein.

糖尿病性脑病（DE）被定义为糖尿病的主要并发症之一，其特征是神经化学和神经退行性改变。但是，目前尚不完全清楚DE的分子机制。在这里，原代海马神经元在体外培养具有高葡萄糖（HG）诱导类糖尿病的作用，并给小鼠链脲佐菌素（STZ）诱导1型糖尿病（T1D）小鼠模型。萝卜硫烷（SF）的给药用于观察对海马神经元的保护作用。我们发现葡萄糖调节蛋白78（GRP78）（一种典型的内质网伴侣）的表达在HG诱导的原代海马神经元和T1D小鼠的早期均呈上升趋势，而在晚期呈下降趋势。然而，SF在体外和体内均抑制了HG诱导的细胞凋亡。通过TUNEL分析和caspase3免疫荧光染色。同时，在体外和体内，SF的施用抑制了HG诱导的海马神经元中CHOP，Bax和p-JNK蛋白的上调以及Bcl-2蛋白的下调。与对照小鼠相比，T1D小鼠的caspase12基因仅在第4周被上调，并且被SF抑制。此外，SF和PX12（硫氧还蛋白（Trx）的抑制剂）的联合给药消除了SF的保护作用。我们得出结论，HG诱导海马神经元内质网应激（ERS）的发展，最终导致神经元凋亡。SF预防ERS并减轻HG诱导的海马神经元凋亡体外和体内。潜在的机制可能与SF通过Trx-1靶蛋白抑制CHOP-Bax / Bcl-2，JNK和caspase12信号通路有关。