Microcirculation morphologically refers to the blood flow in vessels of less than 150 μm in diameter, including arterioles, capillaries and venules, which provides nutrients and removes metabolic byproducts within tissues. Microcirculation dysfunction is involved in the pathological progress of many diseases, such as obesity, hypertension, and insulin resistance. In this study we investigated the effects of magnesium lithospermate B (MLB), an active compound of the traditional Chinese medicine Slavia miltiorrhiza, on the microcirculation dysfunction in rats and the underlying molecular mechanisms. The effects of MLB on microcirculation were assessed in vivo by measuring the hindlimb blood perfusion in dextran-induced microcirculation dysfunction rats and mesentery blood flow in anesthetized rats. We demonstrated that administration of MLB restored the impaired rat hindlimb blood flow and promoted the mesenteric micoperfusion in vivo. We further revealed in these two animal models that MLB treatment significantly increased the production of total nitrite in vascular tissues (mesentery, aorta, and heart), which was confirmed in human microvascular endothelial cells (HMEC-1) treated with MLB in vitro. Moreover, we showed that MLB treatment significantly increased the phosphorylation of endothelium nitric oxide synthase (eNOS) via inducing AKT phosphorylation in vivo and in vitro. Co-administration of the eNOS inhibitor L-NAME (20 mg/kg) abolished the protective effects of MLB against dextran-induced microcirculation dysfunction in rats, whereas pretreatment with PI3K inhibitor LY294002 (10 μM) prevented eNOS activation in MLB-treated HMEC-1 cells. Our results suggest that MLB can restore the microcirculation dysfunction via activating eNOS, and in turn enhancing the vascular nitric oxide production, which is medicated by MLB-caused activation of the PI3K/AKT pathway.

中文翻译：

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Magnesium lithospermate B 通过激活 PI3K/AKT 通路促进血管 NO 产生，从而改善大鼠的微循环灌注。

微循环形态学上是指直径小于150μm的血管中的血流，包括微动脉、毛细血管和小静脉，提供组织内的营养物质并清除代谢副产物。微循环功能障碍参与了肥胖、高血压、胰岛素抵抗等多种疾病的病理进展。在本研究中，我们研究了中药鼠尾草的活性化合物紫草酸镁 B (MLB) 对大鼠微循环功能障碍的影响及其潜在分子机制。通过测量右旋糖酐诱导的微循环功能障碍大鼠的后肢血灌注和麻醉大鼠的肠系膜血流量，评估MLB对微循环的体内影响。我们证明，给予 MLB 可恢复受损的大鼠后肢血流并促进体内肠系膜微灌注。我们进一步在这两种动物模型中发现，MLB 处理显着增加了血管组织（肠系膜、主动脉和心脏）中总亚硝酸盐的产生，这在体外用 MLB 处理的人微血管内皮细胞（HMEC-1）中得到了证实。此外，我们发现，MLB 处理通过诱导体内和体外 AKT 磷酸化，显着增加内皮一氧化氮合酶 (eNOS) 的磷酸化。联合给予 eNOS 抑制剂 L-NAME (20 mg/kg) 消除了 MLB 对大鼠右旋糖酐诱导的微循环功能障碍的保护作用，而用 PI3K 抑制剂 LY294002 (10 μM) 预处理可阻止 MLB 处理的 HMEC 中的 eNOS 激活。 1 个细胞。我们的结果表明，MLB 可以通过激活 eNOS 来恢复微循环功能障碍，进而增强血管一氧化氮的产生，这是通过 MLB 引起的 PI3K/AKT 通路激活来实现的。