Abstract Context Recent studies have shown compound Danshen dripping pills (CDDP) could improve microcirculation in ischemic/reperfusion injury and other microvascular disorders. The mechanism for CDDP’s role in microcirculation is not clear. Objective To explore the protective effects of CDDP on microvascular dysfunction. Materials and methods C57BL/6 male mice (6–8 weeks) were randomized into control, model and CDDP groups (n = 10), which were treated with normal saline or CDDP (105.30 mg/kg), respectively. Then, lipid emulsion and heparin were infused via mice jugular vein to establish systemic microvascular dysfunction model. Coronary flow reserve (CFR) and leukocytes adhesion on microvascular wall were measured. Relative CD11b and CD62L expression levels on neutrophils were measured by flow cytometric analysis. Expression level of forkhead box transcription factor O1 (FOXO1) mRNA was identified by real-time PCR. Results Lipid infusion significantly attenuated the CFR (1.84 ± 0.14 vs. 2.65 ± 0.02) and increased the number of leukocytes adherent to microvascular wall in cremaster (4067.00 ± 581.20 cells/mm2 vs. 10.67 ± 4.81 cells/mm2). The expression level of CD11b and FOXO1 in neutrophils was also up-regulated by lipid infusion. Pre-treatment with CDDP significantly improved CFR (2.57 ± 0.29 vs. 1.84 ± 0.14), decreased the number of leukocytes adherent to microvascular wall (2500.00 ± 288.70 cells/mm2 vs. 4067.00 ± 581.20 cells/mm2) and down-regulated CD11b and FOXO1 expression. Discussion and conclusions: Pre-treatment with CDDP could prevent lipid infusion-induced systemic microvascular disorder including coronary and peripheral microvascular dysfunction. Down-regulated FOXO1 and decreased leukocyte adhesion might play an important role in the mechanisms of CDDP’s efficacy.

中文翻译：

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复方丹参滴丸预处理预防脂质输注所致小鼠微血管功能障碍

摘要 背景最近的研究表明复方丹参滴丸（CDDP）可以改善缺血/再灌注损伤和其他微血管疾病的微循环。CDDP 在微循环中的作用机制尚不清楚。目的探讨CDDP对微血管功能障碍的保护作用。材料和方法 C57BL/6 雄性小鼠（6-8 周）随机分为对照组、模型组和 CDDP 组（n = 10），分别用生理盐水或 CDDP（105.30 mg/kg）治疗。然后通过小鼠颈静脉注入脂质乳剂和肝素，建立全身微血管功能障碍模型。测量冠状动脉血流储备 (CFR) 和微血管壁上的白细胞粘附。通过流式细胞术分析测量嗜中性粒细胞上的相对 CD11b 和 CD62L 表达水平。叉头盒转录因子 O1 (FOXO1) mRNA 的表达水平通过实时 PCR 进行鉴定。结果 脂质输注显着降低了 CFR（1.84 ± 0.14 对 2.65 ± 0.02）并增加了附着在提睾管微血管壁上的白细胞数量（4067.00 ± 581.20 个细胞/mm2 对 10.67 ± 4.81 个细胞/mm2）。中性粒细胞中 CD11b 和 FOXO1 的表达水平也被脂质输注上调。CDDP 预处理显着提高了 CFR（2.57 ± 0.29 与 1.84 ± 0.14），减少了粘附在微血管壁上的白细胞数量（2500.00 ± 288.70 个细胞/mm2 与 4067.00 ± 581.20 个细胞/mm2）并下调了 CD11b FOXO1 表达。讨论和结论：CDDP 预处理可以预防脂质输注引起的全身微血管疾病，包括冠状动脉和外周微血管功能障碍。下调 FOXO1 和减少白细胞粘附可能在 CDDP 的功效机制中发挥重要作用。