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代谢组学与整合药理学揭示 l-薄荷醇对大鼠脑缺血的治疗作用。

Metabolomics coupled with integrative pharmacology reveals the therapeutic effect of l-borneolum against cerebral ischaemia in rats.

机构信息

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

出版信息

J Pharm Pharmacol. 2020 Sep;72(9):1256-1268. doi: 10.1111/jphp.13294. Epub 2020 Jun 4.

Abstract

OBJECTIVES

This study aimed to investigate metabolic biomarker changes and related metabolic pathways before and after treatment with l-borneolum in cerebral ischaemic rats.

METHODS

Rats were subjected to pMCAO surgery. The Zea-Longa scoring method was used to evaluate neurological deficits. TTC staining was used to observe cerebral infarction. HE staining was used to observe the pathological changes in brain tissue. The metabolomics method was used to analyse the changes in metabolism.

RESULTS

The pharmacology changes of the H-B group were significantly different from those of the vehicle group. Moreover, according to the metabolomics method, identification of potential biomarkers in cerebral ischaemia treatment showed that the levels of l-valine and l-arginine were increased while the levels of N-succinyl-L,L-2,6-diaminopimelate and LysoPC (18 : 1(9Z)) were reduced, which were related to energy metabolism. Simultaneously, thermogenesis and bile secretion levels were inhibited by l-borneolum. Furthermore, elevated level of methotrexate might be related to an anti-inflammatory effect.

CONCLUSIONS

The therapeutic effect of l-borneolum on cerebral ischaemia might be associated with the regulation of energy metabolism, thermogenesis and bile secretion. These metabolic changes and the core target changes, as well as the metabolic-target pathway network, help to elucidate the mechanisms governing the effect of l-borneolum on cerebral ischaemia.

摘要

目的

本研究旨在探讨龙脑治疗脑缺血大鼠前后代谢标志物的变化及其相关代谢途径。

方法

大鼠行大脑中动脉阻塞(pMCAO)手术。采用 Zea-Longa 评分法评估神经功能缺损。TTC 染色观察脑梗死。HE 染色观察脑组织病理变化。采用代谢组学方法分析代谢变化。

结果

H-B 组的药理学变化与载体组有显著差异。此外,根据代谢组学方法,鉴定脑缺血治疗中潜在的生物标志物表明,l-缬氨酸和 l-精氨酸的水平升高,而 N-琥珀酰-L,L-2,6-二氨基庚二酸和 LysoPC(18:1(9Z))的水平降低,这与能量代谢有关。同时,龙脑抑制了产热和胆汁分泌水平。此外,甲氨蝶呤水平升高可能与抗炎作用有关。

结论

龙脑对脑缺血的治疗作用可能与能量代谢、产热和胆汁分泌的调节有关。这些代谢变化以及核心靶点变化和代谢-靶点途径网络有助于阐明龙脑对脑缺血的作用机制。

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