自发性高血压大鼠的中医证型特点及其代谢物质基础研究
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甘肃中医药大学

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Observation of Chinese medicine syndrome type and characterization of plasma metabolome in spontaneously hypertensive rats
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Gansu University of Chinese Medicine

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    摘要:

    目的 了解高血压病研究常用病模型动物---自发性高血压大鼠(spontaneously hypertensive rat,SHR)的中医证型特点及可能的代谢物质基础。方法 通过综合动态观察和检测SHR大鼠的一般状态、性情、周围血管充盈度、舌象、饮食和水量摄入、大小便量与性状、血压、心率、呼吸频率、痛阈和旷场实验,以辨别其可能的中医证型。同时,利用高效液相色谱串联质谱联用技术(Liquid Chromatography Tandem-mass Spectrometry, LC-MS/MS)对血清代谢物进行非靶向分析,以初步揭示引起血压升高和中医证型表现的物质基础。结果 与WKY组大鼠相比,SHR毛色暗黄,易激惹状态及周围毛细血管充盈评分明显增高(P≤0.05);舌色赤红,舌质干、津液少;二便及饮食饮水明显减少,粪便含水量较低(P≤0.05);收缩压(systolic blood pressure,SBP)、舒张压(diastolic blood pressure,DBP)、平均动脉压(mean arterial pressure,MAP)、心率(heart rate,HR)、呼吸频率(respiratory rate,RR)均显著升高;痛阈下降;旷场实验显示边缘的运动距离和停留时间增加(P≤0.05)。血清非靶向代谢组学结果显示,与WKY组大鼠相比,SHR具有显著差异的代谢物共有114种(P≤0.05),这些差异代谢物主要为Lipids and lipid-like molecules(40.35%)、Organic acids and derivatives(22.8%)、Organoheterocyclic compounds(15.79%)。差异代谢物通过KEGG富集分析共得到25条代谢通路,进一步差异丰度得分分析,其中16条通路被激活,仅4条通路被抑制,5条通路未见明显变化;而其中与神经系统兴奋性相关的3条通路中,谷氨酸能突触(Glutamatergic Synapse)和γ-氨基丁酸能突触(GABAergic Synapse)被激活,而5-羟色胺能突触(Serotonergic Synapse)则被抑制。结论 SHR有急躁易怒、周围血管扩张侧支循环形成、球结膜充血膨出、舌色赤红,舌质干、便秘、小便少而赤黄、心率、呼吸频率增快等表现,这些均提示SHR表现为高血压肝阳上亢证,其物质基础除了与脂类、氨基酸、碳水化合物代谢增强有关外,还可能和兴奋性神经代谢通路被活化而抑制神经代谢通路被抑制有关。

    Abstract:

    OBJECTIVE To investigate the characteristics of Chinese medicine syndromes and possible metabolic substance basis of spontaneously hypertensive rat (SHR), a common model animal for hypertensive research. METHODS The general state, temperament, peripheral vascular filling, tongue image, diet and water intake, urine and feces volume and characteristics, blood pressure, heart rate, respiratory rate, pain threshold and open field of SHR rats were observed and tested comprehensively to identify the possible syndrome types of Chinese medicine. At the same time, Liquid Chromatography Tandem mass Spectrometry (LC-MS/MS) was used to analyze non-targeted serum metabolites, so as to preliminarily reveal the material basis of blood pressure elevation and Chinese medicine syndrome manifestations. RESULTS Compared with WKY group, SHR was dark yellow, irritable state and peripheral capillary filling score were significantly increased (P≤0.05); Red tongue color, dry tongue, little body fluid; Quantity of feces, urine, diet and drinking water decreased significantly, and the water content of feces was low (P≤0.05); Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR) and respiratory rate (RR) were significantly increased(P≤0.05); Pain threshold decreased(P≤0.05); The open field experiment showed that the moving distance and residence time of the edge increased (P≤0.05). Serum non-targeted metabolomics results showed that compared with WKY group, there were 114 metabolites with significant differences in SHR (P≤0.05). These differential metabolites were mainly Lipids and lips-like molecules (40.35%), Organic acids and derivatives (22.8%), and Organoheterocyclic compounds (15.79%). A total of 25 metabolic pathways were obtained by KEGG enrichment analysis. Further differential abundance analysis showed that 16 pathways were activated, only 4 pathways were inhibited, and 5 pathways were not significantly changed. The Glutamatergic Synapse (Glutamatergic Synapse) and gamma-aminobutyric acid Synapse (GABAergic Synapse) were activated, while the 5-serotonergic synapse (Serotonergic synapse) was inhibited. CONCLUSION The symptoms of SHR include impatience and irritability, peripheral vascular dilation and collateral circulation formation, bulbar conjunctival congestive swelling, red tongue color, dry tongue, constipation, red yellow urine with little urine, rapid heart rate and respiratory rate, etc. All these suggest that SHR is a syndrome of hypertension with hyperactivity of liver-yang. The material basis of SHR is not only related to lipid and amino acid and carbohydrate metabolism disorders, but also may be related to the activation of excitatory neurometabolic pathway and inhibition of inhibitory neurometabolic pathway.

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  • 收稿日期:2024-07-05
  • 最后修改日期:2024-08-30
  • 录用日期:2024-12-02
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