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目的 研究四氢姜黄素(THC)和纳米四氢姜黄素(THCN)的抗抑郁作用及机制。方法 将46只雄性ICR小鼠随机分为Con组、脂多糖(LPS)组、THC组、THCN组和舍曲林(SER)组。采用腹腔注射LPS建立小鼠抑郁模型。采用旷场实验和强迫游泳实验评估小鼠的焦虑及抑郁样行为；髓鞘染色法检测长期实验小鼠前额皮层脱髓鞘程度；免疫荧光法检测短期实验小鼠前额皮层和海马组织中胶质纤维酸性蛋白(GFAP)和Toll样受体4(TLR4)表达水平。结果 与Con组相比，长期和短期实验LPS组小鼠焦虑抑郁样行为均增加(P<0.05);长期实验LPS组小鼠脱髓鞘程度增加(P<0.01);短期实验LPS组小鼠GFAP表达减少(P<0.01),TLR4表达增加(P<0.05),THC组小鼠TLR4表达减少(P<0.01),THCN组前额皮层的GFAP表达减少(P<0.01),TLR4表达增加(P<0.05)。与LPS组相比，长期实验THC组小鼠抑郁样行为减少(P<0.05),THCN组和SER组小鼠焦虑抑郁样行为减少(P<0.05),短期实验THC组、THCN组小鼠焦虑抑郁样行为减少(P<0.05);长期实验THC组、THCN组和SER组小鼠脱髓鞘程度均减少(P<0.05);短期实验THC组GFAP表达增加(P<0.05),TLR4表达减少(P<0.05),THCN组GFAP表达增加(P<0.05)。与THC组相比，长期实验THCN组、SER组焦虑样行为减少(P<0.05);短期实验THCN组前额皮层的GFAP表达减少(P<0.05),海马DG区TLR4表达增加(P<0.01)。结论 THC和THCN均能改善脂多糖诱导的小鼠抑郁样行为和脱髓鞘化，THC的抗抑郁机制可能与下调TLR4、增加GFAP有关，THCN的抗抑郁机制可能与增加GFAP有关。
Abstract：Objective To investigate the antidepressant effects and the underlying mechanisms of tetrahydrocurcumin(THC) and its nanoparticle formulation(THCN). Methods Forty-six male ICR mice were randomly divided into Con group, LPS group, THC group, THCN group and SER group. A mouse depression model was established by intraperitoneal administration of LPS. The anxiety and depression-like behaviors of mice were evaluated by open field test(OFT) and forced swimming test(FST). Myelin staining was applied to assess the extent of demyelination in the prefrontal cortex of the mice. The prefrontal cortex and hippocampus were further examined for the expression levels of glial fibrillary acidic protein(GFAP) and Toll-like receptor 4(TLR4) through quantitative immunofluorescence assays. Results Compared with the Con group, the LPS group showed increased anxiety-like and depressive-like behaviors in both the long-term and short-term experiments(P<0.05); the degree of demyelination increased in the LPS group of the long-term experiment(P<0.01); the expression of GFAP was reduced in the LPS group of the short-term experiment(P<0.01), while the expression of TLR4 increased(P<0.05); the expression of TLR4 decreased in the THC group(P<0.01); the expression of GFAP in the prefrontal cortex of the THCN group was reduced(P<0.01), while the expression of TLR4 increased(P<0.05). Compared with the LPS group, the THC group showed reduced depressive-like behaviors in the long-term experiment(P<0.05), while the anxiety-like and depressive-like behaviors of the THCN group and the SER group were reduced(P<0.05), and the anxiety-like and depressive-like behaviors of the THC group and the THCN group were reduced in the short-term experiment(P<0.05); the degree of demyelination was reduced in the THC group, THCN group and SER group in the long-term experiment(P<0.05); the expression of GFAP increased in the THC group of the short-term experiment(P<0.05), while the expression of TLR4 was reduced(P<0.05), and the expression of GFAP increased in the THCN group(P<0.05). Compared with the THC group, the THCN group and the SER group showed reduced anxiety-like behaviors in the long-term experiment(P<0.05); the expression of GFAP in the prefrontal cortex of the THCN group was reduced in the short-term experiment(P<0.05), while the expression of TLR4 in the hippocampal DG area increased in the short-term experiment(P<0.01). Conclusion Tetrahydrocurcumin and its nanoparticle formulation both exert significant ameliorative effects on depression-like behaviors and demyelination in mice induced by lipopolysaccharide. The antidepressant mechanism of THC appears to be mediated through the down-regulation of TLR4 and the up-regulation of GFAP. The mechanism underlying the antidepressant action of THCN seems predominantly focused on the enhancement of GFAP expression.
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基本信息:
DOI：10.19405/j.cnki.issn1000-1492.2025.01.011
中图分类号:R285.5
引用信息:
[1]谭慧,李远萍,孟靖源等.四氢姜黄素及其纳米制剂对脂多糖诱导的抑郁小鼠的改善作用[J].安徽医科大学学报,2025,60(01):79-86.DOI:10.19405/j.cnki.issn1000-1492.2025.01.011.
基金信息:
国家自然科学基金(编号：82060650); 云南省科技厅科技计划项目(编号：202405AC350045)~~