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赵震宇, 李琳, 胡志希.基于16S rRNA测序和网络药理学方法探讨参附注射液治疗心力衰竭的作用机制[J].湖南中医药大学学报英文版,2025,45(2):239-249.[Click to copy
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| 基于16S rRNA测序和网络药理学方法探讨参附注射液治疗心力衰竭的作用机制 |
| 赵震宇,李琳,胡志希 |
| (湖南中医药大学中医诊断学湖南省重点实验室, 湖南 长沙 410208;湖南中医药大学中医诊断研究所, 湖南 长沙 410208) |
| 摘要: |
| 目的 探讨参附注射液治疗心力衰竭（以下简称“心衰”）的作用机制。方法 30只雄性SD大鼠随机分为空白组（n=7）和造模组（n=23）。造模组大鼠采用异丙肾上腺素皮下注射法（5 mg·kg-1·d-1，连续1周）制备心衰大鼠模型，空白组大鼠经皮下注射等量生理盐水。造模完成后，将成模大鼠随机分为模型组（n=8）和参附组（n=8）。参附组大鼠腹腔注射参附注射液（6 mL·kg-1·d-1，连续1周），空白组和模型组大鼠腹腔注射等量生理盐水。药物干预结束后，于麻醉状态下行心脏超声心动图检测；经腹主动脉取血，收集血液样本检测炎症指标；于结肠段收集粪便样本和结肠组织进行16S rRNA测序和HE染色；摘取大鼠心脏行HE染色。运用网络药理学方法，筛选参附注射液活性成分、靶点及心衰和差异菌群相关靶点，并对相同靶点进行GO功能和KEGG通路富集分析。结果 与空白组比较，模型组大鼠射血分数（EF）、缩短分数（FS）下降（P<0.001），N末端B型利钠肽原（NT-proBNP）升高（P<0.001），脂多糖（LPS）、白细胞介素（IL）-6、IL-1β升高（P<0.001）。与模型组比较，参附组大鼠EF、FS升高（P<0.001），NT-proBNP下降（P<0.001），LPS、IL-6、IL-1β下降（P<0.01，P<0.001）。参附组与空白组的肠道菌群相似度高于模型组与空白组。群落组成和线性判别分析效应量（LEfSe）结果表明，与空白组比较，模型组大鼠多级物种丰度发生改变，上述改变在参附组中呈现回调趋势。网络药理学结果发现，“参附注射液-肠道菌群-心衰”的共同靶点为IL-10、IL-1β、IL-6、肿瘤坏死因子，并且GO功能、KEGG富集分析结果也与炎症反应密切相关。结论 参附注射液可能通过调节肠道菌群，抑制机体炎症反应，进而改善心功能。 |
| 关键词: 参附注射液 心力衰竭 16S rRNA 肠道菌群 网络药理学 异丙肾上腺素 |
| DOI：10.3969/j.issn.1674-070X.2025.02.007 |
| Received:July 31, 2024 |
| 基金项目:国家自然科学基金项目（82274412，82305092）；湖南省自然科学基金项目（2023JJ30453）；湖南省青年科技创新人才项目（2024RC3199）；湖南省中医药科研项目（B2023045）。 |
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| Mechanism of action of Shenfu Injection in treating heart failure based on 16S rRNA sequencing and network pharmacology approaches |
| ZHAO Zhenyu, LI Lin, HU Zhixi |
| (Hunan Provincial Key Laboratory of Chinese Medicine Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;Institute of Chinese Medicne Diagnosis, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China) |
| Abstract: |
| Objective To investigate the mechanism of action of Shenfu Injection in treating heart failure (HF). Methods Thirty male SD rats were randomly divided into blank group (n=7) and modeling group (n=23). Rats in the modeling group were administered subcutaneous injections of isoproterenol (5 mg·kg-1·d-1 for one week) to induce HF, while rats in the blank group received an equal volume of normal saline subcutaneously. After model induction, successfully modeled rats were randomly divided into model group (n=8) and Shenfu group (n=8). Rats in the Shenfu group were treated with Shenfu Injection (6 mL·kg-1·d-1 for one week) via intraperitoneal injection, while rats in the normal and model groups received intraperitoneal injections of an equal volume of normal saline. After drug intervention, echocardiography was performed under anesthesia, blood samples were collected from the abdominal aorta for the detection of inflammatory markers, fecal samples and colon tissues were collected for 16S rRNA sequencing and HE staining, and rats' hearts were excised for HE staining. Network pharmacology methods were used to screen the active components and targets of Shenfu Injection, as well as targets related to HF and differential microbiota, followed by GO function and KEGG pathway enrichment analysis for common targets. Results Compared with the blank group, the rats in the model group showed decreased ejection fraction (EF) and fractional shortening (FS) (P<0.001), and increased N-terminal pro-B-type natriuretic peptide (NT-proBNP) (P<0.001), lipopolysaccharide (LPS), interleukin-6 (IL-6), and interleukin-1β (IL-1β) levels (P<0.001). Compared with the model group, rats in the Shenfu group exhibited increased EF and FS (P<0.001) and decreased NT-proBNP (P<0.001), LPS, IL-6, and IL-1β levels (P<0.01, P<0.001). The intestinal microbiota composition in the Shenfu group was more similar to that of the normal group than to the model group. Community composition and linear discriminant analysis effect size (LEfSe) results indicated that compared with the blank group, the model group rats had altered multi-level species abundance, and these changes showed a trend of recovery in the Shenfu group. Network pharmacology results revealed that the common targets of "Shenfu Injection-intestinal microbiota-HF" were interleukin-10 (IL-10), IL-1β, IL-6, and tumor necrosis factor, and the GO function and KEGG enrichment analyses results were also closely related to the inflammatory response. Conclusion Shenfu Injection may improve cardiac function by regulating the intestinal microbiota and inhibiting the body's inflammatory response. |
| Key words: Shenfu Injection heart failure 16S rRNA intestinal microbiota network pharmacology isoprenaline |
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