柿叶黄酮类化合物对D-半乳糖致衰老小鼠的抗炎抗氧化神经保护作用

 目的  探讨柿叶中黄酮类提取物对D-半乳糖所致衰老小鼠行为学、脑内氧化应激及炎性机制的影响。方法  40只雄性昆明小鼠,随机分为正常对照组(NC组)、模型组(D-gal组)、柿叶黄酮低剂量组(D-gal+F40组)、柿叶黄酮高剂量组(D-gal+F80组)。D-gal组及柿叶黄酮治疗组于颈背部皮下注射D-半乳糖100 mg·kg-1·d-1,连续用药60天建立衰老模型,D-gal+F40组和D-gal+F80组分别以40、80 mg·kg-1·d-1 的柿叶黄酮提取物灌胃干预。NC组与D-gal组以同样方法给予等体积生理盐水。应用Morris水迷宫试验测试各组小鼠逃避潜伏期(escape latency,EL)及穿越平台次数;试剂盒测定小鼠脑组织超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)活性及丙二醛(malondialdehyde,MDA)含量;酶联免疫吸附测定(enzyme-linked immunosorbent assay,ELISA)及免疫组织化学方法检测脑组织炎性因子、肿瘤坏死因子(tumor necrosis factor-alpha,TNF-α)及白介素-1β(interleukin-1beta,IL-1β)的表达。结果  与NC组相比,D-gal组衰老小鼠EL延长、穿越平台次数减少;脑内氧化应激及炎性因子水平显著升高。D-gal+F40组和D-gal+F80组较D-gal组EL明显降低、穿越平台次数显著增加;脑组织SOD、GSH-Px活性升高,MDA含量降低;同时炎性因子TNF-α和IL-1β的表达减少。结论  柿叶黄酮类化合物能够明显改善亚急性衰老小鼠学习记忆能力,提高脑组织的抗氧化能力,降低脑内炎症水平,具有延缓脑衰老的作用。

Neuroprotective effects of flavonoids extracted from the leaves of Diospyros kaki in D-galactose induced aging mice by attenuating oxidative stress and neuroinflammation

Objective  To investigate the effects of flavonoids extracted from the leaves of Diospyros kaki on praxiology and the possible mechanisms involving oxidative stress and inflammation of the brain in aging mice induced by D-galactose.Methods  Forty Kunming male mice were randomly divided into four groups:normal control group (NC group),model group (D-gal group),low-dose flavonoids intervention group (D-gal+F40 group) and large-dose flavonoids intervention group (D-gal+F 80 group).D-gal group and two intervention groups received injection of D-galactose 100 mg·kg-1·d-1
for 60 days to build aging model.D-gal+F40 group and D-gal+F 80 group were fed with flavonoids 40 and 80 mg·kg-1·d-1 respectively by oral gavage,while NC group and D-gal group were fed with the same volume of normal saline.Morris water maze was used for testing escape latency (EL) and the number of crossing,related kits were used for detecting superoxide dismutase (SOD) activity,glutathione peroxidase (GSH-Px) activity and malondialdehyde (MDA) content in the brain tissue,enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were used for detecting the expression of inflammation factors,tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β).Results  Compared with NC group,EL elevated,the number of crossings decreased,oxidative stress and inflammatory cytokines levels increased significantly in D-galactose induced aging mice.Compared with D-gal group,flavonoids extracted from Diospyros kaki obviously decreased EL,increased the number of crossings,increased SOD,GSH-Px activity and decreased MDA content,reduced the expression of TNF-α and IL-1β in D-gal+F40 group and D-gal+F80 group.Conclusions  Flavonoids from leaves of Diospyros kaki could obviously improve cognitive function in subacute aging mice induced by D-galactose.It also improved the antioxidant ability,lowered inflammation levels in the brain with the function of delaying brain aging.