补阳还五汤治疗大鼠气虚血瘀型脑缺血的代谢组学研究
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国家重点基础研究发展计划(973计划)项目(2015CB554400)——基于病证结合的气血相关理论研究;中国中医科学院科技创新工程项目(CI2021A04614)——基于胶质淋巴系统的治疗脑水肿中药脑细胞间液药理学研究


Metabonomics of Buyang Huanwu Decoction in the Rat Model of Cerebral Ischemia with Syndrome of Qi Deficiency and Blood Stasis
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    摘要:

    目的:探讨补阳还五汤对气虚血瘀型脑缺血大鼠生物代谢途径的影响。方法:将30只大鼠随机分为假手术组、模型组和补阳还五汤组(3.49 g/kg)。模型组和补阳还五汤组采用荧光微球诱导多发性脑梗死合并睡眠剥夺,建立气虚血瘀型脑缺血动物模型,并分别给予蒸馏水或补阳还五汤灌胃。假手术组给予蒸馏水灌胃,不睡眠剥夺和微球注射。记录各组大鼠的体质量。实验结束后,处死大鼠,采血分析。酶联免疫吸附试验法检测大鼠血清中血栓素B2(TXB2)和6-酮基-前列环素1α(6-keto-PGF1α)水平。采用液质联用的代谢组学方法检测血清样品。结果:与假手术组比较,模型组大鼠平均体质量明显降低,TXB2/6-keto-PGF1α比值升高(均P<0.05);与模型组比较,补阳还五汤组大鼠平均体质量升高,药物干预可降低TXB2/6-keto-PGF1α比值(P<0.05)。代谢组学结果显示,假手术组与模型组比较,差异有统计学意义(P<0.05),补阳还五汤组部分逆转模型组的变化,指标向假手术组回调的趋势明显。结论:模型大鼠体内的生物代谢途径受到明显干扰,补阳还五汤可以对异常生物代谢途径进行明显的调整,其调整的代谢途径包括:精氨酸的生物合成、精氨酸和脯氨酸代谢、谷胱甘肽代谢、赖氨酸的生物合成。

    Abstract:

    To explore the effects of Buyang Huanwu Decoction on the metabolic pathways in the rat model of cerebral ischemia with the syndrome of qi deficiency and blood stasis.Methods:Thirty rats were randomized into sham operation,model,and Buyang Huanwu Decoction(3.49 g/kg) groups.The rat model was established by injection of fluorescent microspheres combined with sleep deprivation.The rats in the model and Buyang Huanwu Decoction groups were administrated with distilled water and Buyang Huanwu Decoction,respectively.The rats in the sham operation group were subjected to neither sleep deprivation nor microsphere injection,except administration with distilled water.The body weights of rats in each group were recorded.After the experiment,rats were sacrificed and the blood was sampled.The enzyme-linked immunosorbent assay was employed to measure the levels of thromboxane B2(TXB2) and 6-keto-prostacyclin1α(6-keto-PGF1α) in the serum.The metabonomics method based on LC-MS was employed to detect the serum samples.Results:The average body weight in the model group was lower than that in the sham operation group and the Buyang Huanwu Decoction group.Compared with the sham operation group,the model group showed increased TXB2/6-keto-PGF1α ratio(P<0.05),and drug intervention reduced such increase(P<0.05).There was a significant difference in the metabolome between the sham operation group and the model group(P<0.05).Buyang Huanwu Decoction partially reversed the changes caused by modeling.Conclusion:The metabolic pathways in the model rats were significantly disturbed.Buyang Huanwu Decoction can adjust the abnormal metabolic pathways,including arginine biosynthesis,arginine and proline metabolism,glutathione metabolism,and lysine biosynthesis.

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宋文婷,丁昭,苗兰,孙明谦,尹春园,曹慧,史跃,马彦雷,李磊,刘建勋.补阳还五汤治疗大鼠气虚血瘀型脑缺血的代谢组学研究[J].世界中医药,2023,(15).

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  • 收稿日期:2022-07-05
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  • 在线发布日期: 2023-08-21
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