Emergency Center, Affilated Hospital of Dalian Medical University, Dalian 116011, China.
World J Emerg Med. 2011;2(3):228-31. doi: 10.5847/wjem.j.1920-8642.2011.03.013.
Sepsis is a tough problem in critical ill patients. This study aimed to investigate the dynamic changes of monocyte Toll-like receptor (TLR) 4 expression in peripheral blood of septic rats and to determine the effects of transforming growth factor (TGF)-β1 on TLR4 expression.
Altogether 132 clean level SD rats were randomly divided into a control group (n=12), a sepsis model group (n=60), and a TGF-β1 intervention group (n=60). In the sepsis model group and TGF-β1 intervention group, the rats were subdivided into five groups (2-hour group, 6-hour group, 12-hour group, 24-hour group, and 48-hour group), with 12 rats in each group. Cecal ligation puncture (CLP) was performed in the sepsis model group and TGF-β1 intervention group to establish models of sepsis. The rats in the sepsis model group were injected with 1 mL normal saline at the caudal vein 0.5 hour after the model establishment; the rats in the TGF-β1 intervention group were injected with 20 ng/mL or 250 g TGF-β1 0.5 hour after the model establishment. Flow cytometry was used to detect the change of monocyte TLR4 in peripheral blood, and enzyme-linked immunosorbent assay (ELISA) was used to detect the change of TNF-α level in peripheral blood.
At 6-12 hours after CLP, the monocyte TLR4 in peripheral blood started to decrease, and reached the lowest level at 12 hours. Compared to the control group, the monocyte TLR4 expression at 6 and 12 hours was lowered significantly (P<0.05). Compared to the sepsis model group at 2, 24 and 48 hours after CLP, the monocyte TLR4 expression in the TGF-β1 intervention group decreased dramatically (P<0.05), but there were no differences between the two groups at 6 and 12 hours respectively. Compared to the control group, the concentration of NF-κ in liver tissue increased significantly 6 hours after CLP (P<0.05). After use of TGF-β1, the concentration of NF-κ was decreased significantly but still higher than that of the control group. Compared to the control group, the concentration of TNF-α in peripheral blood was increased significantly at 2-48 hours after CLP (P<0.05). After use of TGF-β1, TNF-α was further increased.
During sepsis, TGF-β1 can decrease the monocyte TLR4 expression and NF-κ in liver tissue, but facilitate the formation of proinflammatory mediator TNF-α. This finding indicates that TGF-β1 may play a role in promoting inflammatory response during sepsis, but this regulation is not via direct regulation of monocyte TLR4 in peripheral blood.
脓毒症是危重病患者的一个难题。本研究旨在探讨脓毒症大鼠外周血单核细胞 Toll 样受体（TLR）4 表达的动态变化，并确定转化生长因子（TGF）-β1 对 TLR4 表达的影响。
将 132 只清洁级 SD 大鼠随机分为对照组（n=12）、脓毒症模型组（n=60）和 TGF-β1 干预组（n=60）。脓毒症模型组和 TGF-β1 干预组再分为 5 个亚组（2 小时组、6 小时组、12 小时组、24 小时组和 48 小时组，每组 12 只）。通过盲肠结扎穿孔（CLP）建立脓毒症模型。脓毒症模型组于模型建立后 0.5 小时尾静脉注射 1 mL 生理盐水；TGF-β1 干预组于模型建立后 0.5 小时注射 20 ng/mL 或 250μg TGF-β1。采用流式细胞术检测外周血单核细胞 TLR4 的变化，酶联免疫吸附试验（ELISA）检测外周血 TNF-α 水平的变化。
CLP 后 6-12 小时，外周血单核细胞 TLR4 开始下降，12 小时达到最低水平。与对照组相比，6 小时和 12 小时 TLR4 表达明显降低（P<0.05）。与 CLP 后 2、24 和 48 小时的脓毒症模型组相比，TGF-β1 干预组 TLR4 表达明显下降（P<0.05），但 6 小时和 12 小时两组之间无差异。CLP 后 6 小时，肝组织中 NF-κ 的浓度明显升高（P<0.05）。使用 TGF-β1 后，NF-κ 的浓度明显下降，但仍高于对照组。与对照组相比，CLP 后 2-48 小时外周血 TNF-α 浓度明显升高（P<0.05）。使用 TGF-β1 后，TNF-α 进一步增加。
脓毒症时，TGF-β1 可降低肝组织中单核细胞 TLR4 和 NF-κ 的表达，但促进促炎介质 TNF-α 的形成。这一发现表明，TGF-β1 可能在脓毒症期间通过促进炎症反应发挥作用，但这种调节不是通过外周血单核细胞 TLR4 的直接调节。
