虾青素对D-半乳糖致衰老小鼠认知功能障碍的改善作用及机制研究

Ameliorating effects and mechanism of astaxanthin on D-galactose-induced cognitive dysfunction in aging mice

中文关键词:  虾青素  认知功能  p38丝裂原活化蛋白激酶  衰老

英文关键词:astaxanthin  cognitive function  p38 mitogen-activated protein kinase  aging

中文摘要:

      目的 探究虾青素改善D-半乳糖致衰老小鼠认知功能的作用及作用机制。方法 采用随机数表法将小鼠分为正常组、模型组、虾青素低剂量组、虾青素中剂量组、虾青素高剂量组。除正常组外, 其余各组均给予腹腔连续注射D-半乳糖, 采用腹腔注射D-半乳糖构建衰老小鼠模型。通过水迷宫实验观察各组小鼠学习记忆能力的变化情况; 采用分光光度法测定小鼠脑组织中丙二醛(malondialdehyde, MDA)和谷胱甘肽(glutataione, GSH)的含量以及超氧化物歧化酶(superoxide dismutase, SOD)的活性; 通过酶联免疫吸附(enzyme linked immunosorbent assay, ELISA)法检测小鼠血清中白细胞介素-6 (interleukin-6, IL-6)和肿瘤坏死因子-α (tumor necrosis factor-α, TNF-α)的表达水平; 通过免疫印记法检测小鼠脑中突触素(synaptophysin, SYN)、突触后致密物-95 (postsynaptic density-95, PSD-95)、p38丝裂原活化蛋白激酶(p38 mitogen-activated protein kinase, p38MAPK)和磷酸化p38丝裂原活化蛋白激酶(phosphorylated p38 mitogen activated protein kinase, p-p38)的表达水平。结果 行为学实验结果显示, 虾青素各剂量组对于D-半乳糖致衰老小鼠认知功能障碍均有改善作用, 并且存在剂量依赖性。生物学检测结果显示, 虾青素可以降低衰老小鼠脑组织中MDA的含量, 升高GSH的含量, 并且提高SOD的活性; 降低小鼠血清中IL-6和TNF-α的表达水平, 提示虾青素可以通过抗氧化和抗炎, 改善D-半乳糖致衰老小鼠引起的认知功能障碍。此外, 蛋白质免疫印迹(Western Blot, WB)结果显示, 给予虾青素干预后, 衰老小鼠脑中突触相关蛋白SYN和PSD-95的表达水平显著提升, p-p38蛋白的表达水平显著降低, 提示虾青素可以通过抑制p38MAPK信号通路的过度激活, 改善突触可塑性。结论 虾青素对D-半乳糖致衰老小鼠认知功能障碍具有改善作用, 其作用机制可能与抑制p38MAPK信号通路过度激活, 抗氧化、抗炎和改善突触可塑性有关。

英文摘要:

      Objective To explore the improvement effect and mechanism of astaxanthin on D-galactose-induced cognitive dysfunction in aging mice. Methods The mice were divided into normal group, model group, low-dose astaxanthin group, middle-dose astaxanthin group, and high-dose astaxanthin group by random number table method. Except for the normal group, the other groups were given continuous intraperitoneal injection of D-galactose, and the aging mouse model was established by intraperitoneal injection of D-galactose. The changes of learning and memory ability of mice in each group were detected by water maze test. The content of malondialdehyde (MDA) and glutathione (GSH) and the activity of superoxide dismutase (SOD) in mouse brain tissues were detected by spectrophotometry. The levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in serum of mice were detected by enzyme linked immunosorbent assay (ELISA). Expression levels of synaptophysin (SYN), postsynaptic density-95 (PSD-95), p38 mitogen-activated protein kinase (p38MAPK) and phosphorylated p38 mitogen-activated protein kinase (p-p38) in mouse brains were detected by immunoblotting. Results The results of behavioral experiments showed that all dose groups of astaxanthin could improve the cognitive dysfunction of aging mice induced by D-galactose in a dose-dependent manner. The biological test results showed that astaxanthin could reduce the content of MDA, increase the content of GSH and increase the activity of SOD in the brain tissues of aging mice; reduce the levels of IL-6 and TNF-α in serum of mice, suggesting that astaxanthin could improve the cognitive dysfunction caused by D-galactose-induced aging mice through antioxidant and anti-inflammatory. In addition, Western Blot (WB) results showed that astaxanthin could significantly increase the levels of synapse-related proteins SYN and PSD-95 in the brain of aging mice and reduce the expression level of p-p38 protein, suggesting that astaxanthin could improve synaptic plasticity by inhibiting the over activation of p38MAPK signal pathway. Conclusion Astaxanthin can improve cognitive dysfunction in aging mice induced by D-galactose, and its mechanism of action may be related to inhibiting excessive activation of p38MAPK signaling pathway, anti-oxidation, anti-inflammatory and improving synaptic plasticity.