Department of Pulmonology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Shock. 2013 Mar;39(3):317-25. doi: 10.1097/SHK.0b013e318283773e.
The aim of the present study was to examine the effect and possible mechanism of salvianolic acid B (SalB) on pulmonary microcirculation disturbance induced by lipopolysaccharide (LPS) in rat. Male Sprague-Dawley rats were subjected to thoracotomy under continuous anesthesia and mechanical ventilation. Albumin leakage from pulmonary capillary and the numbers of leukocytes adherent to the pulmonary capillary wall were determined for 60 min by an upright microscope upon LPS (2 mg · kg(-1) · h(-1)) infusion with or without administration of SalB (5 mg · kg(-1) · h(-1)). Pulmonary tissue wet-to-dry weight ratio, tumor necrosis factor α, and interleukin 8 in plasma and bronchoalveolar lavage fluid were measured. In addition, the expressions of E-selectin, intercellular adhesion molecule 1, and myeloperoxidase in pulmonary tissue were assessed by immunohistochemistry. The expressions of aquaporin 1 (AQP-1), AQP-5, metalloproteinase 2 (MMP-2), and MMP-9 were assessed by Western blot assay. Pretreatment with SalB significantly attenuated LPS-induced pulmonary microcirculatory disturbance, including the increase in leukocyte adhesion and albumin leakage. In addition, LPS increased pulmonary tissue wet-to-dry weight ratio and tumor necrosis factor α and interleukin 8 levels in plasma and bronchoalveolar lavage fluid enhanced the expression of E-selectin, intercellular adhesion molecule 1, myeloperoxidase, MMP-2, and MMP-9, whereas it decreased the expression of AQP-1 and AQP-5 in pulmonary tissue, all of which were attenuated by SalB pretreatment. Salvianolic acid B pretreatment improves pulmonary microcirculation disturbance and lung injury on LPS exposure. More studies are required to evaluate the potential of SalB as an option for protecting lung from endotoxemia.
本研究旨在探讨丹参多酚酸(SalB)对脂多糖(LPS)诱导的大鼠肺微循环障碍的作用及可能机制。雄性 Sprague-Dawley 大鼠在持续麻醉和机械通气下行开胸术。通过在 LPS(2 mg·kg(-1)·h(-1))输注的同时或不给予 SalB(5 mg·kg(-1)·h(-1)),使用直立显微镜测定肺毛细血管白蛋白漏出和白细胞黏附于肺毛细血管壁的数量,持续 60 min。测量血浆和支气管肺泡灌洗液中肺组织湿重/干重比、肿瘤坏死因子α和白细胞介素 8。此外,通过免疫组织化学评估肺组织中 E-选择素、细胞间黏附分子 1 和髓过氧化物酶的表达。通过 Western blot 测定水通道蛋白 1(AQP-1)、AQP-5、基质金属蛋白酶 2(MMP-2)和 MMP-9 的表达。SalB 预处理显著减轻 LPS 诱导的肺微循环障碍,包括白细胞黏附和白蛋白漏出增加。此外,LPS 增加了血浆和支气管肺泡灌洗液中肺组织湿重/干重比以及肿瘤坏死因子α和白细胞介素 8 的水平,增强了 E-选择素、细胞间黏附分子 1、髓过氧化物酶、MMP-2 和 MMP-9 的表达,而降低了肺组织中 AQP-1 和 AQP-5 的表达,所有这些都被 SalB 预处理所减弱。SalB 预处理可改善 LPS 暴露所致的肺微循环障碍和肺损伤。需要更多的研究来评估 SalB 作为保护肺免受内毒素血症的选择的潜力。