目的:运用血清代谢组学的方法探索引火汤(Yinhuo Tang)对卵巢摘除(OVX)联合慢性不可预见性轻度应激(CUMS)小鼠抑郁样行为改善作用的机制。方法:45只昆明小鼠随机分为假手术组(sham组)、去卵巢模型组(OVX+CUMS组)和引火汤组,采用OVX+CUMS复制绝经后抑郁症(PMD)模型。旷场试验和强迫游泳试验观察小鼠的抑郁样行为;HE染色观察各组小鼠海马神经元状态;利用代谢组学方法观察各组小鼠体内血清差异代谢产物的变化,并分析其内在的生物学意义。结果:行为学结果显示,引火汤给药后OVX+CUMS小鼠的抑郁样行为明显改善;HE染色结果显示,引火汤给药后海马神经元形态呈正常现象。代谢组学研究结果显示,引火汤给药后小鼠血液的代谢轮廓均有显著的回调趋势,共鉴定差异代谢产物11个,包括柠檬酸、蒎酸、鞘磷脂、鞘氨醇1-磷酸、前列腺素J2、α-二吗啉酸、(S)-3-羟基丁酸、磷脂酰肌醇、对甲酚葡糖苷酸、对甲酚硫酸盐和酪氨酸有明显回调作用。结论:引火汤能够改善OVX+CUMS诱导抑郁小鼠的抑郁样行为,其作用机制可能是通过调节亚油酸代谢、柠檬酸循环、鞘脂代谢、谷氨酸代谢、乙醛酸和类固醇激素生物合成代谢通路实现的。
Objective: To study the mechanism of Yinhuo Tang in improving depression like behavior in ovariectomized (OVX) combined with chronic unpredictable mild stress (CUMS) mice was explored by using the method of serum metabolomics. Methods: Forty-five Kunming mice were randomly divided into sham operation group, ovariectomy model group and Yinhuo Tang group. OVX+CUMS were used to replicate the postmenopausal depression (PMD) model. Open field test and forced swimming test were used to observe the depression like behavior of mice. HE staining was used to observe the state of hippocampal neurons in each group. Metabonomics method was used to observe the changes of serum differential metabolites in each group of mice, and its internal biological significance was analyzed. Results: The behavioral results showed that the depression like behavior of OVX+CUMS mice was significantly improved after administration of Yinhuo Tang. HE staining showed that the morphology of hippocampal neurons was normal. The results of metabonomics study showed that the metabolic profile of blood in mice after administration of Yinhuo Tang had a significant callback trend, and a total of 11 differential metabolites were identified, including citric acid, pinellic acid, sphingomyelin, sphingosine 1-phosphate, prostaglandin J2, alpha-dimorphecolic acid, (S)3-hydroxybutyric acid, PI[16∶0/22∶4 (10Z, 13Z, 16Z, 19Z)], p-cresol glucuronide, p-cresol sulfate and tyrosine, which had obvious callback effects. Conclusion: Yinhuo Tang can improve the depression like behavior of OVX+CUMS induced depression mice, and its mechanism may be achieved by regulating linoleic acid metabolism, citric acid cycle, sphingolipid metabolism, glutamate metabolism, glyoxylic acid and steroid hormone biosynthesis metabolic pathway.
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