亚精胺可抑制高血糖诱导的神经元衰老，为脑病提供治疗新方法

日积月累的高血糖会引发神经毒性和脑衰老，补充亚精胺可有效避免神经毒副作用

【文献解读】

南华大学神经科学研究所唐小卿教授课题组研究发现，在高糖处理的小鼠海马神经元细胞中，亚精胺通过上调大麻素1型受体（CB1）阻止了神经细胞活力的丧失和衰老，为糖尿病性脑病的预防和治疗提供了新的方法。该研究发表于Clinical and Experimental Pharmacology and Physiology杂志。

研究人员选择了小鼠海马神经元细胞HT-22，在其培养基中添加不同浓度的葡萄糖进行研究。研究人员发现，处理48小时后，细胞活力呈剂量依赖性降低，含衰老标志物β-半乳糖苷酶的细胞比例和衰老相关蛋白的表达水平均显著升高。这表明高糖诱导了HT-22细胞的神经毒性和细胞衰老。研究人员用亚精胺预处理HT-22细胞半小时，再经高糖处理后发现，细胞活力显著增加，衰老细胞数降低。CB1受体被认为是中枢神经系统的保护蛋白，研究人员发现，亚精胺可以通过上调CB1受体来预防高糖诱导的神经毒性。

高血糖引起的神经毒性与糖尿病性脑病和神经元衰老有关。本研究的发现表明亚精胺可能作为高血糖诱导衰老的潜在治疗剂。

【文献节选】

Hyperglycaemia-induced neurotoxicity involved in the pathogenesis of diabetic encephalopathy and neuronal senescence is one of the worst effects of hyperglyceamic neurotoxicity. Cannabinoid receptor type 1 (CB1) has neuroprotective function in a series of neuropathy. Spermidine (Spd) has anti-aging function in many tissues. However, the role of Spd in hyperglyceamia-induced neuronal senescence remains unexplored. Therefore, we used high glucose (HG)-treated HT-22 cell as vitro model to investigate whether Spd protects neurons against hyperglyceamia-induced senescence and the mediatory role of CB1 receptor. The HT-22 cells were cultured in HG condition in the presence of different dose of Spd. Then, the viability of cells was measured by Cell Counting Kit-8 (CCK-8) assay. The senescence of cells was detected by Senescence-associated β-galactosidase (SA-β-Gal) staining. The expressions of p16INK4a, p21CIP1 and CB1 receptor were measured by western blot. We found that Spd inhibited HG-induced neurotoxicity (the loss of cell viability) and senescence (the increase of SA-β-Gal positive cells, the upregulation of p16INK4a and p21CIP1) in HT-22 cells. Also, Spd prevented HG-induced downregulation of CB1 receptor in HT-22 cells. Furthermore, we demonstrated that AM251 (a specific inhibitor of the CB1 receptor) reversed the protective effects of Spd on HG-induced neurotoxicity and senescence. These results indicated that Spd prevents HG-induced neurotoxicity and senescence via the upregulation of CB1 receptor. Our findings provide a promising future of Spd-based preventions and therapies for diabetic encephalopathy.