Abstract：
BACKGROUND: Naoxintong capsule (NXT) is a compound traditional Chinese medicine prescription with demonstrated effect for the treatment of cardiovascular and cerebrovascular diseases including atherosclerosis (AS). However, the pharmacological mechanisms of NXT in ameliorating early-stage AS are still unclear, especially regarding the role of gut microbiota.
OBJECTIVE: This study is aiming to evaluate the therapeutic effect of NXT against early-stage AS, and further illustrate the potential correlations among AS, gut microbiota, and NXT.
METHODS: Thirty-two male ApoE knockout mice (C57BL/6 background) were fed with a high cholesterol diet (HCD) for 4 weeks to establish an early-stage AS model. NXT in two different dosages and simvastatin (Simv) were than administrated for another 8 weeks. Lipid metabolism indicators and inflammation levels were measured with corresponding assay kits. Changes in blood vessels, liver lesions, and intestinal barrier proteins were evaluated with different staining methods. Furthermore, the gut microbiota structure was analyzed using 16S rRNA sequencing technology, while GC-MS was utilized to determine the fecal contents of short-chain fatty acids (SCFAs).
RESULTS: Administration of NXT significantly ameliorated obesity, hyperlipidemia, systemic inflammation, vasculopathy, liver injury, and intestinal barrier disorder in AS mice. Administration of NXT also significantly regulated the gut microbiota disturbance and increased the total contents of fecal SCFAs in AS mice. Furthermore, acetic acid content and the relative abundance of Faecalibacterium in feces were proposed as potential therapeutic biomarkers of NXT for AS treatment as indicated via the correlation analysis.
CONCLUSIONS: This study demonstrated that NXT could effectively treat early-stage AS induced by HCD in mice. NXT regulated the gut microbiota and metabolites, maintained intestinal homeostasis, and improved the systemic inflammatory response. These findings may provide robust experimental support for the clinical use of NXT for AS treatment.
OBJECTIVE: This study is aiming to evaluate the therapeutic effect of NXT against early-stage AS, and further illustrate the potential correlations among AS, gut microbiota, and NXT.
METHODS: Thirty-two male ApoE knockout mice (C57BL/6 background) were fed with a high cholesterol diet (HCD) for 4 weeks to establish an early-stage AS model. NXT in two different dosages and simvastatin (Simv) were than administrated for another 8 weeks. Lipid metabolism indicators and inflammation levels were measured with corresponding assay kits. Changes in blood vessels, liver lesions, and intestinal barrier proteins were evaluated with different staining methods. Furthermore, the gut microbiota structure was analyzed using 16S rRNA sequencing technology, while GC-MS was utilized to determine the fecal contents of short-chain fatty acids (SCFAs).
RESULTS: Administration of NXT significantly ameliorated obesity, hyperlipidemia, systemic inflammation, vasculopathy, liver injury, and intestinal barrier disorder in AS mice. Administration of NXT also significantly regulated the gut microbiota disturbance and increased the total contents of fecal SCFAs in AS mice. Furthermore, acetic acid content and the relative abundance of Faecalibacterium in feces were proposed as potential therapeutic biomarkers of NXT for AS treatment as indicated via the correlation analysis.
CONCLUSIONS: This study demonstrated that NXT could effectively treat early-stage AS induced by HCD in mice. NXT regulated the gut microbiota and metabolites, maintained intestinal homeostasis, and improved the systemic inflammatory response. These findings may provide robust experimental support for the clinical use of NXT for AS treatment.
摘要：
背景：脑心通胶囊（NXT）是一种治疗包括动脉粥样硬化（AS）在内的心脑血管疾病的中药复方。然而,NXT改善早期AS的药理机制尚不清楚，尤其是关于肠道微生物群的作用。
目的：本研究旨在评估NXT对早期AS的治疗效果。并进一步说明了AS之间的潜在相关性，肠道菌群，NXT。
方法：32只雄性ApoE基因敲除小鼠（C57BL/6背景）饲喂高胆固醇饮食（HCD）4周，建立早期AS模型。以两种不同剂量的NXT和辛伐他汀(Simv)再给药8周。用相应的测定试剂盒测量脂质代谢指标和炎症水平。血管的变化,肝脏病变,用不同的染色方法评价肠屏障蛋白。此外，使用16SrRNA测序技术分析肠道菌群结构，同时利用GC-MS测定粪便中短链脂肪酸（SCFA）的含量。
结果：服用NXT可显着改善肥胖，高脂血症,全身性炎症,血管病变,肝损伤,和AS小鼠的肠屏障障碍。NXT的给药还显着调节了AS小鼠的肠道微生物群紊乱并增加了粪便SCFA的总含量。此外，如通过相关性分析所指示的,提出了粪便中粪杆菌的乙酸含量和相对丰度作为用于AS治疗的NXT的潜在治疗性生物标志物。
结论：本研究证明NXT能有效治疗HCD诱导的小鼠早期AS。NXT调节肠道微生物群和代谢产物，维持肠道稳态，改善全身炎症反应。这些发现可能为NXT用于AS治疗的临床应用提供有力的实验支持。
目的：本研究旨在评估NXT对早期AS的治疗效果。并进一步说明了AS之间的潜在相关性，肠道菌群，NXT。
方法：32只雄性ApoE基因敲除小鼠（C57BL/6背景）饲喂高胆固醇饮食（HCD）4周，建立早期AS模型。以两种不同剂量的NXT和辛伐他汀(Simv)再给药8周。用相应的测定试剂盒测量脂质代谢指标和炎症水平。血管的变化,肝脏病变,用不同的染色方法评价肠屏障蛋白。此外，使用16SrRNA测序技术分析肠道菌群结构，同时利用GC-MS测定粪便中短链脂肪酸（SCFA）的含量。
结果：服用NXT可显着改善肥胖，高脂血症,全身性炎症,血管病变,肝损伤,和AS小鼠的肠屏障障碍。NXT的给药还显着调节了AS小鼠的肠道微生物群紊乱并增加了粪便SCFA的总含量。此外，如通过相关性分析所指示的,提出了粪便中粪杆菌的乙酸含量和相对丰度作为用于AS治疗的NXT的潜在治疗性生物标志物。
结论：本研究证明NXT能有效治疗HCD诱导的小鼠早期AS。NXT调节肠道微生物群和代谢产物，维持肠道稳态，改善全身炎症反应。这些发现可能为NXT用于AS治疗的临床应用提供有力的实验支持。
