| 基于血清代谢组学探究川芎-香附药对调控色氨酸通路治疗偏头痛的作用机制 |
| 投稿时间：2024-09-11 修订日期：2024-10-08 点此下载全文
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| 基金项目:国家自然科学基金（82474380）；北京市教育委员会科研计划项目（KM202210025020）；北京市属高校教师队伍建设支持计划优秀青年人才项目（BPHR202203112） |
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| 中文摘要:目的：基于血清代谢组学探究川芎-香附药对治疗偏头痛的作用机制。方法：雄性SD大鼠,皮下注射硝酸甘油建立急性偏头痛模型,随机分为对照组、模型组、阳性药组、川芎-香附组、川芎组、香附组。腹主动脉取血,分离血清和脑干组织,超高效液相色谱串联质谱进行血清代谢组学分析,筛选差异代谢物和差异代谢通路。使用Metscape插件构建代谢物-反应-酶-基因网络,分析差异性代谢物和差异性代谢通路的靶基因。RT-PCR检测色氨酸羟化酶2(TPH2)mRNA表达,ELISA检测TPH2和5-羟色胺(5-HT)含量。结果：各组大鼠血清代谢轮廓存在明显差异,川芎-香附、川芎、香附治疗偏头痛的差异性代谢物分别有25、7、13个,川芎-香附抗偏头痛的差异性代谢通路是泛醌和其他萜醌类生物合成、生物素代谢、色氨酸代谢,川芎抗偏头痛的差异性代谢通路是生物素代谢,香附抗偏头痛的差异性代谢通路是色氨酸代谢。色氨酸代谢通路的关键靶基因是TPH2,其参与5-HT代谢。验证实验发现,模型组大鼠脑干中TPH2 mRNA、TPH2、5-HT表达显著降低,川芎-香附组、香附组可显著升高TPH2 mRNA、TPH2和5-HT含量,川芎组升高TPH2 mRNA、TPH2和5-HT但不显著。结论：川芎-香附药对通过调控色氨酸代谢及其下游靶基因TPH2的表达而促进5-HT的合成,实现治疗偏头痛的配伍增效作用。 |
| 中文关键词:川芎 香附 偏头痛 代谢组学 色氨酸 |
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| Mechanism of the herb pair of Chuanxiong-Xiangfu on regulating tryptophan metabolism pathway in the treatment of migraine based on serum metabolomics |
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| Abstract:Objective: To explore the mechanism of the herb pair of Chuanxiong-Xiangfu in the treatment of migraine based on serum metabolomics. Methods: Male SD rats were divided into control group, model group, positive drug group, Chuanxiong-Xiangfu group, Chuanxiong group, and Xiangfu group. All rats expect those in the control group received subcutaneous injection with nitroglycerin injections to induce an acute migraine model. Blood was collected from the abdominal aorta. Serum was analyzed by metabolomics through ultra-performance liquid chromatography mass spectrometry. A compound–reaction–enzyme–gene network was constructed by the Metscape plugin for screening the differentially expressed metabolites and metabolic pathways. Brainstem tissues were isolated for detecting the mRNA expression of tryptophan hydroxylase 2 (TPH2) by RT-PCR, and the levels of TPH2 and 5-hydroxytryptamine (5-HT) by ELISA. Results: There were significant differences in the serum metabolic profiles among all the groups. 25, 7, and 13 differentially expressed metabolites were identified for Chuanxiong-Xiangfu, Chuanxiong, and Xiangfu in treating migraine, respectively. Ubiquinone and other terpenoid-quinone biosynthesis, biotin metabolism and tryptophan metabolism were identified as the key metabolic pathways for Chuanxiong-Xiangfu against migraine. Biotin metabolism was identified as the key metabolic pathway for Chuanxiong against migraine. Tryptophan metabolism was identified as the key metabolic pathway for Xiangfu against migraine. TPH2, which is involved in 5-HT metabolism, is the key target gene of tryptophan metabolic pathway. Validation experiments found that TPH2 mRNA, TPH2 content, and 5-HT content were significantly decreased in the brainstem tissues of migraine rats. Chuanxiong-Xiangfu group and Xiangfu group significantly increased the TPH2 mRNA, TPH2 content, and 5-HT content. Chuanxiong group elevated TPH2 mRNA, TPH2 and 5-HT, but it was not significant. Conclusion: The herb pair of Chuanxiong-Xiangfu promoted the synthesis of 5-HT by regulating tryptophan metabolism and its downstream target gene of TPH2, which displayed a synergistic effect for treating migraine. |
| keywords:Chuanxiong Xiangfu migraine metabolomics tryptophan |
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