| 李天华,李春晨,张翠红,等.姜黄素调节核转录因子红系 2相关因子 2/血红素加氧酶 -1/ NAD(P)H脱氢酶醌 1通路对围绝经期抑郁症大鼠神经损伤的保护作用机制[J].安徽医药,2026,30(7):1327-1332. |
| 姜黄素调节核转录因子红系 2相关因子 2/血红素加氧酶 -1/ NAD(P)H脱氢酶醌 1通路对围绝经期抑郁症大鼠神经损伤的保护作用机制 |
| The protective mechanism of curcumin on neurodegeneration in peri-menopausal depressive rats by regulating the Nrf2/HO-1/NQO1 signaling pathway |
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| DOI：10.3969/j.issn.1009-6469.2026.07.011 |
| 中文关键词: 姜黄素 核因子红细胞系 2相关因子 2 围绝经期 抑郁症 氧化应激 炎性损伤 大鼠， Sprague-Dawley |
| 英文关键词: Curcumin Nuclear factor erythroid 2-related factor 2 Perimenopause Depression disorder Oxidative stress In-flammatory damage Rats, Sprague-Dawley |
| 基金项目:河北省医学科学研究项目( 20221660) |
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| 中文摘要: |
| 目的探讨姜黄素通过调控核因子红细胞系 2相关因子 2(Nrf2)/血红素加氧酶 -1(HO-1)/NAD(P)H脱氢酶醌 1(NQO1)通路对围绝经期抑郁症(PMD)大鼠神经损伤的影响和分子机制。方法研究时间为 2024年 2—7月，将 54只 SPF级 SD大鼠分为假手术组、模型组、阳性对照组、姜黄素低剂量( CUR-L)组、姜黄素高剂量( CUR-H)组、通路抑制剂组(CUR-H+ML385组)，每组 9只。在治疗期间观察大鼠的一般情况，通过糖水偏好实验、强迫游泳实验、旷场实验等对各组大鼠行为学进行评估，留取各组大鼠脑组织，苏木精 -伊红( HE)染色和尼氏染色观察脑组织神经细胞形态，末端脱氧核糖核苷酸转移酶介导的 dUTP缺口末端标记法( TUNEL)染色检测神经细胞凋亡，试剂盒检测氧化应激相关分子［丙二醛、超氧化物歧化酶( SOD)、过氧化氢酶(CAT)］水平，酶联免疫吸附分析( ELISA)检测炎性因子［白细胞介素( IL)-1β、IL-6、IL-4、IL-10、肿瘤坏死因子 α(TNF-α)］水平，检测 Nrf2、HO-1/NQO1的蛋白表达。结果与假手术组相比，模型组大鼠出现行为学改变，表现为精神不振、活动减少、糖水偏好率下降［(81.47±8.96)%比(32.11±3.24)%］不动时间延长。组织实验中，相对于假手术组，模型组大鼠脑组织病理损伤明显，神经细胞和尼氏小体减少，细胞凋亡增加，同时、伴有 CAT［(112.14±12.31)kU/L比( 41.23±4.35)kU/L］、 SOD［(100.11±10.23)kU/L比(38.76±4.58)kU/L］水平下降和丙二醛水平增加，促炎因子水平升高， Nrf2、HO-1、NQO1蛋白水平降低(均 P<0.05)。与模型组比较，阳性对照组以及姜黄素处理组上述指标显著改善(均 P<0.05)但姜黄素对 PMD模型大鼠各指标的改善作用被 ML385部分逆转(均 P<0.05)。结论姜黄素通过调节 Nrf2/HO-1/NQO1信号通路，进而改善 PMD大鼠脑组织氧化应激和炎性损伤。 |
| 英文摘要: |
| Objective To investigate the effects and molecular mechanisms of curcumin on neural injury in perimenopausal depres-sion (PMD) rats by regulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/NAD(P)H dehydrogenase quinone 1 (NQO1) pathway.Methods The study was conducted from February to July 2024. Fifty-four SPF-grade SD rats were divid-ed into six groups (n=9 per group): sham operation group, model group, positive control group, curcumin low dose (CUR-L) group, cur.cumin high dose (CUR-H) group, and pathway inhibitor group (CUR-H+ML385 group). General conditions of rats were observed duringtreatment. Behavioral assessments were performed using sucrose preference test, forced swimming test, and open field test. Brain tis-sues were collected for hematoxylin-eosin (HE) staining and Nissl staining to observe neuronal morphology. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was used to detect neuronal apoptosis. Oxidative stress-related mole-cules [malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT)] were measured by assay kits. Inflammatory factors[interleukin (IL) -1β, IL-6, IL-4, IL-10, and tumor necrosis factor α (TNF-α)] were detected by enzyme-linked immunosorbent assay (ELISA). Protein expressions of Nrf2, HO-1, and NQO1 were detected.Results Compared with the sham operation group, rats in themodel group exhibited behavioral changes including listlessness, reduced activity, decreased sucrose preference rate [(81.47±8.96) % vs. (32.11±3.24) %], and prolonged immobility time. Histologically, the model group showed obvious pathological damage in brain tis-sue, reduced neurons and Nissl bodies, increased cell apoptosis, accompanied by decreased CAT[(112.14±12.31)kU/L vs. (41.23±4.35) kU/L] and SOD[(100.11±10.23)kU/L vs. (38.76±4.58)kU/L] levels, increased MDA levels, elevated pro-inflammatory factors, and de-creased protein levels of Nrf2, HO-1, and NQO1 (all P<0.05). Compared with the model group, the positive control group and curcumin-treated groups showed significant improvement in the above indicators (all P<0.05), whereas the ameliorative effects of curcumin on PMD model rats were partially reversed by ML385 (all P<0.05).Conclusion Curcumin improves oxidative stress and inflammatory in-jury in brain tissue of PMD rats by regulating the Nrf2/HO-1/NQO1 signaling pathway. |
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