Department of Cardiovascular Surgery, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China.
Chin Med J (Engl). 2012 May;125(10):1753-9.
Bacterial lipopolysaccharide (LPS) can activate immunological cells to secrete various proinflammatory cytokines involved in the pathophysiological process of disseminated intravascular coagulation (DIC) during infection. In recent years, it has been found that bone marrow-derived mesenchymal stem cells (BMSCs) can affect the activity of these immune cells and regulate the secretion of proinflammatory cytokines. Here, we report the possible protective effect of BMSCs pre-treatment in LPS-induced DIC rat model and the mechanism.
Forty-eight adult male rats were divided into five experimental groups and one control group with eight animals in each group. In the treatment groups, 0, 1'10(6), 2'10(6), 3'10(6), and 5'10(6) of BMSCs were injected intravenously for 3 days before LPS injection, while the control group was treated with pure cell culture medium injection. Then, the LPS (3 mg/kg) was injected via the tail vein in the treatment groups, while the control group received 0.9% NaCl. Blood was withdrawn before and 4 and 8 hours after LPS administration. The following parameters were monitored: platelets (PLT), fibrinogen (Fib), D-dimer (D-D), activated partial thromboplastin time (APTT), prothrombin time (PT), tumor necrosis factor-a (TNF-a), interferon-g (IFN-g), interleukin-1b (IL-1b), creatinine (Cr), alanine aminotransferase (ALT), creatinine kinase-MB (CK-MB), and endothelin (ET).
Compared with the control group, a significant change of coagulation parameters were found in the experimental groups. The plasma level of the inflammatory mediator (TNF-a, IFN-g, IL-1b), organ indicator (Cr, ALT, and CK-MB), and ET in the experimental groups were much lower (P < 0.05) than that in the control group. Furthermore, some of these effects were dose-dependent; the statistical comparison of the plasma levels between the groups (from group 2 to group 5) showed a significant difference (P < 0.05), except the ALT and CK-MB levels (P > 0.05).
Pre-treatment with BMSCs can attenuate organ dysfunction and inhibit systemic intravascular coagulation effectively via the regulatory effect on immune cells and proinflammatory cytokines in LPS-induced DIC rat model.
细菌脂多糖（LPS）可激活免疫细胞，使其分泌各种参与感染时弥散性血管内凝血（DIC）病理生理过程的促炎细胞因子。近年来，研究发现骨髓间充质干细胞（BMSCs）可影响这些免疫细胞的活性并调节促炎细胞因子的分泌。本研究旨在探讨 BMSCs 预处理对 LPS 诱导的 DIC 大鼠模型的可能保护作用及其机制。
48 只成年雄性大鼠随机分为五组，每组 8 只。预处理组于 LPS 注射前 3 天分别经尾静脉注射 0、1'10(6)、2'10(6)、3'10(6)和 5'10(6)个 BMSCs，对照组给予单纯细胞培养液注射。然后，LPS（3mg/kg）尾静脉注射，对照组给予 0.9%生理盐水。于 LPS 给药前及给药后 4、8 小时采血，监测血小板（PLT）、纤维蛋白原（Fib）、D-二聚体（D-D）、活化部分凝血活酶时间（APTT）、凝血酶原时间（PT）、肿瘤坏死因子-α（TNF-α）、干扰素-γ（IFN-γ）、白细胞介素-1β（IL-1β）、肌酐（Cr）、丙氨酸氨基转移酶（ALT）、肌酸激酶同工酶-MB（CK-MB）和内皮素（ET）。
与对照组相比，实验组凝血参数明显改变。实验组炎症介质（TNF-α、IFN-γ、IL-1β）、器官标志物（Cr、ALT、CK-MB）和 ET 水平均显著低于对照组（P<0.05）。此外，这些作用具有一定的剂量依赖性；组间比较（从第 2 组到第 5 组）血浆水平差异有统计学意义（P<0.05），除 ALT 和 CK-MB 水平外（P>0.05）。
BMSCs 预处理可通过调节 LPS 诱导的 DIC 大鼠模型中的免疫细胞和促炎细胞因子，有效减轻器官功能障碍和抑制全身血管内凝血。
