| 摘要: |
| 目的 探讨脂肪因子代谢对冠状动脉微血管功能障碍（MVD）的影响及麝香通心滴丸（STDP）的临床应用价值。方法 纳入2018年9月至2019年12月上海交通大学医学院附属新华医院心内科收治的41例冠心病患者，分为非MVD组（20例）和MVD组（21例）；29例MVD患者随机分为基础治疗组（14例）和STDP组（15例），分别进行为期3个月的基础治疗和基础治疗加STDP治疗；分析各组患者主诉、血生物化学指标、血浆炎症因子及脂肪因子水平的变化。采用12～14周龄雄性C57BL/6小鼠制备心肌缺血再灌注（IR）模型，分为假手术组、IR组（生理盐水灌胃）和IR＋STDP组（STDP灌胃），每组5只，采用ELISA测定血浆炎症因子水平，通过硫黄素-S荧光密度法测定心脏组织微血管阻塞情况，采用蛋白质组学分析探寻IR组与IR＋STDP组间差异表达蛋白质并通过蛋白质印迹法进行验证。结果 与非MVD组比较，MVD组血浆瘦素水平增高［（9.89±2.42）μg/L vs （4.76±1.02）μg/L，P＜0.01］，脂联素水平下降［（5.02±1.30）pg/mL vs （7.19±1.76）pg/mL，P＜0.05），抵抗素水平升高［（9.20±2.03）μg/L vs （5.70±1.32）μg/L，P＜0.05］。Pearson相关分析显示血浆瘦素水平与微循环阻力呈正相关（r＝0.82，P＜0.01）。ROC曲线分析结果显示，根据血浆瘦素水平判断MVD的AUC值为0.855，最佳临界值为＞9.395 μg/L，灵敏度为0.714，特异度为0.867。MVD患者治疗3个月后，相较于基础治疗组，STDP组主诉胸闷、胸痛症状改善率较高［73.3%（11/15） vs 21.4% （3/14）］，血浆瘦素、IL-6、TNF-α水平均降低［（11.36±0.54）μg/L vs （12.12±0.85）μg/L、（3.96±1.76）pg/mL vs （8.65±1.29）pg/mL、（24.82±3.07）ng/mL vs （32.45±3.32）ng/mL，均P＜0.05］。在动物实验中，与IR组相比，IR＋STDP组小鼠IR术后无回流面积减少45%（P＜0.01）、低回流及无回流面积减少23%（P＜0.05），血浆IL-6、TNF-α水平均下降［（378.25±19.66）pg/mL vs （457.32±32.01）pg/mL、（289.71±47.62）pg/mL vs （371.28±41.05）pg/mL，均P＜0.05］。蛋白质组学分析结果显示，IR＋STDP组小鼠心脏组织中血管性血友病因子（vWF）、细胞间黏附分子-1（ICAM-1）蛋白质表达水平低于IR组，蛋白质印迹法验证结果亦提示IR＋STDP组vWF及ICAM-1蛋白质表达较IR组下调（均P＜0.01）。结论 MVD患者存在脂肪因子代谢异常，血浆瘦素水平较高。STDP治疗可改善MVD患者的临床症状，降低血浆瘦素水平和炎症指标，机制可能与其抗血小板、抗炎作用有关。 |
| 关键词: 微血管功能障碍 冠状动脉 麝香通心滴丸 瘦素 脂肪因子代谢 抗炎 |
| DOI：10.16781/j.CN31-2187/R.20240008 |
| 投稿时间：2024-01-04修订日期：2024-05-07 |
| 基金项目: |
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| Impact of adipokine metabolism on coronary microvascular dysfunction and clinical application value of Shexiang Tongxin dropping pills |
| WU Yuanhao1△,LIN Yanjun2△,FU Hongliang3,MENG Shu2* |
(1. Clinical Medicine School, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200029, China;
2. Department of Cardiology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200029, China;
3. Department of Radiology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200029, China
△Co-first authors.
* Corresponding author) |
| Abstract: |
| Objective To explore the impact of adipokine metabolism on coronary microvascular dysfunction (MVD) and the clinical application value of Shexiang Tongxin dropping pill (STDP). Methods From Sep. 2018 to Dec. 2019, 41 patients with coronary heart disease in Department of Cardiology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were enrolled and divided into non-MVD group (20 cases) and MVD group (21 cases); 29 MVD patients were randomly divided into basic treatment group (14 cases) and STDP group (15 cases) with basic treatment or additional STDP treatment for 3 months; and the patient’s complaints, blood biochemical indicators, expression levels of plasma inflammatory factors and adipokines were analyzed. A myocardial ischemia-reperfusion model was established in male C57BL/6 mice aged 12-14 weeks. Mice were divided into sham operation group, ischemia-reperfusion (IR) group (normal saline gavage), and IR＋STDP group (STDP gavage), with 5 mice in each group. The levels of plasma inflammatory factors were measured by enzyme-linked immunosorbent assay, the microvascular occlusion of the heart tissue was measured by thioflavin-S staining, and the differential expression proteins between the IR group and IR＋STDP group were explored by proteomics analysis and verified by Western blotting. Results Compared with the non-MVD group, the MVD group showed a significant increase in plasma leptin level (［9.89±2.42］ μg/L vs ［4.76±1.02］ μg/L, P＜0.01), a significant decrease in adiponectin level (［5.02±1.3］ pg/mL vs ［7.19±1.76］ pg/mL, P＜0.05), and a significant increase in resistin level (［9.20±2.03］ μg/L vs ［5.70±1.32］ μg/L, P＜0.05). Pearson correlation analysis showed a positive correlation between leptin levels and MVD (r＝0.82 and P＜0.01). Receiver operating characteristic curve analysis showed that the area under curve value of plasma leptin was 0.855 (sensitivity 0.714, specificity 0.867, and optimal cutoff value ＞9.395 μg/L). After 3 months of treatment, compared with the basic treatment group, the improvement rates of symptoms of chest distress and chest pain in the STDP group were significantly higher (73.3% ［11/15］ vs 21.4% ［3/14］), and the levels of plasma leptin, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were significantly lower (［11.36±0.54］ μg/L vs ［12.12±0.85］ μg/L, ［3.96±1.76］ pg/mL vs ［8.65±1.29］ pg/mL, ［24.82± 3.07］ ng/mL vs ［32.45±3.32］ ng/mL, all P＜0.05). In animal studies, compared with the IR group, the mice in the IR＋STDP group showed a 45% reduction in no-reflow area (P＜0.01) and a 23% reduction in low-reflow and no-reflow areas (P＜0.05) after myocardial ischemia-reperfusion; the expression levels of IL-6 and TNF-α were significantly decreased (［378.25± 19.66］ pg/mL vs ［457.32±32.01］ pg/mL, ［289.71±47.62］ pg/mL vs ［371.28±41.05］ pg/mL, both P＜0.05). Proteomic analysis showed that the expression levels of von Willebrand factor (vWF) and intercellular cell adhesion molecule-1 (ICAM-1) in the cardiac tissue of mice in the IR＋STDP group were significantly lower than those in the IR group. Western blotting results also showed that the expression levels of vWF and ICAM-1 in the IR＋STDP group were significantly lower than those in the IR group (both P＜0.01). Conclusion MVD patients have abnormal adipokine metabolism and high plasma leptin. STDP can improve clinical symptoms of MVD patients, reduce the plasma leptin level and inflammatory indicators, and the mechanism may be related to its antiplatelet and anti-inflammatory effects. |
| Key words: microvascular dysfunction coronary artery Shexiang Tongxin dropping pills leptin adipokine metabolism anti-inflammation |
