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Archive > Volume 15 Issue 3 > 2023,15(3):430-438. DOI:https://doi.org/10.1016/j.chmed.2022.12.010 Prev Next

基于LC-MS/MS代謝組學(xué)技術(shù)的龍血通絡(luò)膠囊對缺血性腦中風(fēng)的神經(jīng)保護(hù)作用

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Neuroprotective effects of Longxue Tongluo Capsule on ischemic stroke rats revealed by LC-MS/MS-based metabolomics approach

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    摘要:
    目的：研究龍血通絡(luò)膠囊（LTC）對缺血性腦中風(fēng)大鼠的保護(hù)作用，并探討其潛在機(jī)制。 方法：建立大鼠大腦中動脈阻塞（MCAO）模型模擬臨床上缺血性腦中風(fēng)，通過神經(jīng)癥狀評分、腦缺血面積、組織學(xué)評估驗(yàn)證LTC功效?；赨HPLC-Q Exactive MS的非靶向代謝組學(xué)方法對大鼠大鼠代謝物研究，結(jié)合多元統(tǒng)計分析方法挖掘給藥前后明顯變化的差異代謝物，并對其進(jìn)行代謝通路分析。 結(jié)果：LTC可降低MCAO大鼠的神經(jīng)行為異常評分，顯著降低腦梗死面積。LTC給藥后，大腦皮層梗死區(qū)、核心區(qū)和邊緣區(qū)的膠質(zhì)細(xì)胞和神經(jīng)元的間質(zhì)水腫、萎縮和固縮得到改善。共挖掘到13種潛在的生物標(biāo)志物，其中LysoPC、SM和PE等11種生物標(biāo)志物的Youden指數(shù)均大于0.7。 結(jié)論：相關(guān)性分析和通路分析表明，LTC通過調(diào)節(jié)甘油磷脂和鞘脂代謝、雙煙酰胺和煙酰胺代謝保護(hù)缺血性腦中風(fēng)大鼠。熱圖和三元分析表明，LTC中的黃酮類物質(zhì)可能與碳水化合物和脂質(zhì)發(fā)生協(xié)同作用。

    Abstract:
    Objective: The present study aimed to evaluate the therapeutic effect and explore the underlying mechanisms of Longxue Tongluo Capsule (LTC) on ischemic stroke rats. Methods: Twenty-six rats were randomly divided into four groups, including sham group, sham + LTC group, MCAO group, and MCAO + LTC group. Ischemic stroke rats were simulated by middle cerebral artery occlusion (MCAO), and LTC treatment group were orally administrated with 300 mg/kg of LTC once daily for seven consecutive days. LTC therapy was validated in terms of neurobehavioral abnormality evaluation, cerebral infarct area, and histological assessments. The plasma metabolome comparisons amongst different groups were conducted by UHPLC-Q Exactive MS in combination with subsequent multivariate statistical analysis, aiming to finding the molecules in respond to the surgery or LTC treatment. Results: Intragastric administration of LTC significantly decreased not only the neurobehavioral abnormality scores but also the cerebral infarct area of MCAO rats. The interstitial edema, atrophy, and pyknosis of glial and neuronal cells occurred in the infarcted area, core area, and marginal area of cerebral cortex were improved after LTC treatment. A total of 13 potential biomarkers were observed, and Youden index of 11 biomarkers such as LysoPC, SM, and PE were more than 0.7, which were involved in neuroprotective process. The correlation and pathway analysis showed that LTC was beneficial to ischemic stroke rats via regulating glycerophospholipid and sphingolipid metabolism, together with nicotinate and nicotinamide metabolism. Heatmap and ternary analysis indicated the synergistic effect of carbohydrates and lipids may be induced by flavonoid intake from LTC. Conclusion: The present study could provide evidence that metabolomics, as systematic approach, revealed its capacity to evaluate the holistic efficacy of TCM, and investigate the molecular mechanism underlying the clinical treatment of LTC on ischemic stroke.

    關(guān)鍵詞:
    缺血性腦中風(fēng);龍血通絡(luò)膠囊;代謝組學(xué);大腦中動脈阻塞;酚類化合物;UHPLC-Q Exactive MS

    Keywords:


    Project Supported:
    This work was financially supported by the National Natural Science Foundation of China (81573572, 81530097, 32101957), the National Key R&D Program of China（2022YFC2010104）, Agricultural Science and Technology Innovation Program of Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences (CAAS-ASTIP-Q2022-IFST-08).

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