目的 探讨红花黄色素(SY)对阿尔茨海默病(Alzheimer′s disease AD)转基因小鼠皮层组织炎症损伤的影响。方法 选用6月龄APP/PS1雄性转基因小鼠,随机分成5组:模型组、加兰他敏组、红花黄色素10、30、100 mg·kg-1剂量组,同月龄野生型小鼠作为对照。连续3个月给予相应药物灌胃治疗后,进行Morris水迷宫实验。采用ELISA试剂盒测定各组小鼠皮层中白介素(IL-1β、IL-4、IL-10)、γ-干扰素(IFN-γ)及诱导型一氧化氮合酶(iNOS)的表达。结果 与野生型小鼠比较,模型组小鼠学习记忆能力下降,白介素-1β、干扰素-γ和诱导型一氧化氮合酶水平增加(P<0.01),白介素-4、白介素-10水平下降(P<0.01)。经红花黄色素治疗后,红花黄色素30 mg·kg-1剂量组学习记忆能力显著改善(P<0.01),其对白介素-1β、干扰素-γ、诱导型一氧化氮合酶的表达下调和对白介素-4和白介素-10的表达上调有显著性差异(P<0.01)。红花黄色素 10,100 mg·kg-1剂量组对干扰素-γ、和诱导型一氧化氮合酶的表达下调和对白介素-10的表达上调有显著性差异(P<0.01),其中高剂量组白介素-4水平显著上升(P<0.01),两组对白介素-1β的表达均无显著差异。结论 红花黄色素可以提高痴呆小鼠的学习记忆能力,同时对皮层炎症损伤具有一定程度的保护作用。
Abstract
OBJECTIVE To observe the influence of safflower yellow(SY) on inflammatory injury in cortex of APP/PS1 double Alzheimer′s disease(AD) transgenic mice.METHODS Six-month-old APP/PS1 transgenic male mice were used in the study.The mice were randomly divided into five groupsmodel group, galanthamine group,high,middle and low dose groups of Safflower Yellow,and wild-type mice with same age were selected into normal control group. Each group mice were performed Morris water maze test after given different drugs by gavage for three months. The level of IL-1β, IL-4, IL-10, IFN-γ and iNOS in cortex were detected by ELISA. RESULTS Compared with wild-type controls, the ability of learning and memory were decreased in the model group. The level of IL-1β, IFN-γ and iNOS increased as well as the expression of IL-4, IL-10 decreased(P<0.01). After SY treatment, the learning and memory abilities of middle dose group were elevated (P<0.01); it could obviously down-regulate the expression of IL-1β, IFN-γ, iNOS and up-regulate the expression of IL-4 and IL-10 (P<0.01). High and low dose groups could obviously down-regulate the expression of IFN-γ, iNOS and up-regulate the expression of IL-10 (P<0.01). High dose group does had obvious effect of up-regulating the expression of IL-4 (P<0.01), Both of High and low dose groups didn′t have statistical significance on the expression of IL-1β.CONCLUSION Safflower Yellow could improve the ability of learning and memory and exert protective effects on inflammation damage in the cortex of APP/PS1 transgenic mice.
关键词
红花黄色素 /
阿尔茨海默病 /
炎症因子 /
转基因小鼠
{{custom_keyword}} /
Key words
Safflower Yellow(SY) /
Alzheimer′s disease(AD) /
inflammatory factors /
transgenic mice
{{custom_keyword}} /
中图分类号：
R965
{{custom_clc.code}}
({{custom_clc.text}})
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] PARK S Y, PARK T G, LEE S J, et al. α-Iso-cubebenol inhibits inflammation-mediated neurotoxicity and amyloid beta 1-42 fibril-induced microglial activation[J]. J Pharm Pharmacol, 2014, 66(1):93-105.
[2] MOSHER K I, WYSS-CORAY T. Microglial dysfunction in brain aging and Alzheimer's disease[J]. Biochem Pharmacol, 2014, 88(4):594-604.
[3] FAN S, LIN N, SHAN G, et al. Safflower yellow for acute ischemic stroke:A systematic review of randomized controlled trials[J]. Complement Ther Med, 2014, 22(2):354-361.
[4] YANG X Y, REN Y F. Progress in studies on pharmacological effects of safflower yellow[J]. J Trop Med (热带医学杂志), 2015,15(3):421-424.
[5] MA Q, XU H, RUAN Y Y, et al. Effects of safflower yellower on learning and memory disorders of dementia rats induced by Aβ1-42[J]. Pharmacol Clin Chin Mater Med (中药药理与临床), 2014,36(5):64-66.
[6] XU H, MA Q, WANG Z X, et al. Effects of safflower yellow on D-galactose / sodium nitrite induced learning and memory disorders in mice[J]. Pharmacol Clin Chin Mater Med (中药药理与临床), 2013,35(2):59-61.
[7] LI Y,TAN M S,JIANG T, et al. Microglia in Alzheimer′s disease[J]. Bio Med Res Int, 2014, 2014(2):437483
[8] MORALES I, GUZMN-MARTNEZ L, CERDA-TRONCOSO C, et al. Neuroinflammation in the pathogenesis of Alzheimer′s disease. A rational framework for the search of novel therapeutic approaches[J]. Front Cell Neurosci, 2014, 8:112. doi:10. 3389/fncel. 2014. 00112.
[9] ESSA M M, SUBASH S, AKBAR M, et al. Long-term dietary supplementation of pomegranates, figs and dates alleviate neuroinflammation in a transgenic mouse model of Alzheimer's disease[J]. PLoS One, 2015, 10(3):e0120964.
[10] MINOGUE A M, JONES R S, KELLY R J, et al. Age-associated dysregulation of microglial activation is coupled with enhanced blood-brain barrier permeability and pathology in APP/PS1 mice[J]. Neurobiol Aging, 2014, 35(6):1442-1452.
[11] LATTA C H, SUDDUTH T L, WEEKMAN E M, et al. Determining the role of IL-4 induced neuroinflammation in microglial activity and amyloid-β using BV2 microglial cells and APP/PS1 transgenic mice[J]. J Neuroinflammation, 2015, 12(1):41. doi:10. 1186/s12974-015-0243-6.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
基金
国家自然科学基金资助项目(81360495);兵团博士资金专项资助课题(2013BB016)
{{custom_fund}}
PDF(583 KB)
