Study on the mechanism of curcumin to reduce the inflammatory response of temporal lobe in Alzheimer's disease by regulating miR-146a
Study on the mechanism of curcumin to reduce the inflammatory response of temporal lobe in Alzheimer's disease by regulating miR-146a
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DOI：
10.23736/s0026-4806.20.06463-0
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发表时间：
2022-02-01
期刊：
影响因子：
4.7
通讯作者：
Sun, Derong
中科院分区：
文献类型：
--
作者：
Gong, Jingfeng;Sun, Derong
背景：探讨姜黄素治疗阿尔茨海默病(AD)的可能机制，阐明miR-146a在AD神经炎性反应中的作用。方法：临床病例研究：收集本院神经内科20例AD患者和20例年龄性别匹配的非炎症性和非痴呆患者，采集外周静脉血和脑脊液。用实时荧光定量聚合酶链式反应检测外周血和脑脊液中mir-146a的水平。动物实验研究组：APP/PSI小鼠对照组、APP/PSI小鼠小剂量姜黄素治疗组、C57B1/6J小鼠野生型(WT)对照组，每组10只。用实时荧光定量聚合酶链式反应检测小鼠脑组织中MIR-146a的水平。结果：AD组小鼠血浆miRNA-146a水平为39.10+/-12.97fmol/L，对照组为60.54+/-13.16fmol/L，AD组血浆miRNA-146a水平显著低于对照组。AD组脑脊液miRNA-146a水平(25.16+/-5.16fmol/L)显著高于对照组(11.35+/-3.58fmol/L)。小剂量姜黄素治疗后，APP/PS1小鼠的miRNA-146a水平显著降低，Western印迹法检测到小鼠颞叶Aβ和APP/PS1的表达显著降低，IL-1β和iNOS蛋白水平显著降低，CFH蛋白显著增加。结论：miRNA-146a可作为AD的潜在生物标志物之一。小剂量姜黄素可显著降低神经前炎性miR-146a水平，上调CFH蛋白表达，抑制M1小胶质细胞表型，通过促进Aβ的吞噬和清除机制发挥治疗AD的作用。
BACKGROUND: To explore the potential mechanism of curcumin in the treatment of Alzheimer's disease (AD) and clarify the role of miR-146a in the neuroinflammatory response to AD.METHODS: Clinical case study: 20 AD patients and 20 age-gender matched non-inflammatory and non-dementia patients in the department of neurology of our hospital were included, peripheral venous blood and cerebrospinal fluid were collected. and mir-146a levels in peripheral blood and cerebrospinal fluid were detected by real-time fluorescence quantitative PCR. Animal experimental study group: There were 3 groups, including APP/PSI mice control group, APP/PSI mice low-dose curcumin treatment group, and C57B1/6J mice wild-type (WT) control group, with 10 mice in each group. mir-146a levels in mice brain tissue were detected by quantitative real-time PCR. A beta, APP, complement factor H (CFH) and M1 microglia labeled 1L-1 beta and iNOS in temporal lobe tissues of mice were detected by using Westernblot method.RESULTS: The plasma miRNA-146a level in AD group was 39.10 +/- 12.97 fmol/L, and that in control group was 60.54 +/- 13.16 fmol/L. The plasma miRNA-146a level in AD group was significantly lower than that in control group. The level of miRNA-146a in cerebrospinal fluid of AD group (25.16 +/- 5.16 fmol/L) was significantly higher than that of control group (11.35 +/- 3.58 fmol/L). After treatment with low dose curcumin, the level of miRNA-146a in APP/PS1 mice decreased significantly, and the expression of A beta and APP/PS1 in temporal lobe of mice detected by Western blot decreased significantly, the levels of IL-1 beta and iNOS protein decreased significantly, and the protein of CFH increased significantly.CONCLUSIONS: miRNA-146a can be used as one of the potential biomarkers of AD. Low dose curcumin can significantly reduce the level of neuropro-inflammatory miR-146A, up-regulate the expression of CFH protein, inhibit the phenotype of M1 microglia, and play a role in the treatment of AD by promoting the phagocytosis and clearance mechanism of A beta.