高葡萄糖通过 ROS 和 NF-κB 通路刺激大鼠小胶质细胞中 TNFα 和 MCP-1 的表达。
High glucose stimulates TNFα and MCP-1 expression in rat microglia via ROS and NF-κB pathways.
机构信息
Department of Physiology and Pathophysiology, School of Basic Medical Science, Peking University, Beijing, China.
出版信息
Acta Pharmacol Sin. 2011 Feb;32(2):188-93. doi: 10.1038/aps.2010.174.
AIM
To investigate whether high glucose stimulates the expression of inflammatory cytokines and the possible mechanisms involved.
METHODS
ELISA and real-time PCR were used to determine the expression of the inflammatory factors, and a chemiluminescence assay was used to measure the production of reactive oxygen species (ROS).
RESULTS
Compared to low glucose (10 mmol/L), treatment with high glucose (35 mmol/L) increased the secretion of tumor necrosis factor (TNF)α and monocyte chemotactic protein-1 (MCP-1), but not interleukin (IL)-1β and IL-6, in a time-dependent manner in primary cultured rat microglia. The mRNA expression of TNFα and MCP-1 also increased in response to high glucose. This upregulation was specific to high glucose because it was not observed in the osmotic control. High-glucose treatment stimulated the formation of ROS. Furthermore, treatment with the ROS scavenger NAC significantly reduced the high glucose-induced TNFα and MCP-1 secretion. In addition, the nuclear factor kappa B (NF-κB) inhibitors MG132 and PDTC completely blocked the high glucose-induced TNFα and MCP-1 secretion.
CONCLUSION
We found that high glucose induces TNFα and MCP-1 secretion as well as mRNA expression in rat microglia in vitro, and this effect is mediated by the ROS and NF-κB pathways.
目的
探讨高糖是否刺激炎症细胞因子的表达及其可能涉及的机制。
方法
采用 ELISA 和实时 PCR 测定炎症因子的表达，化学发光法测定活性氧（ROS）的产生。
结果
与低糖（10 mmol/L）相比，高糖（35 mmol/L）刺激原代培养大鼠小胶质细胞中肿瘤坏死因子（TNF）α和单核细胞趋化蛋白-1（MCP-1）的分泌呈时间依赖性增加，但不增加白细胞介素（IL）-1β和 IL-6 的分泌。TNFα和 MCP-1 的 mRNA 表达也随高糖而增加。这种上调是高糖特异性的，因为在渗透控制中观察不到。高糖刺激 ROS 的形成。此外，ROS 清除剂 NAC 的处理显著降低了高糖诱导的 TNFα和 MCP-1 分泌。此外，核因子 kappa B（NF-κB）抑制剂 MG132 和 PDTC 完全阻断了高糖诱导的 TNFα和 MCP-1 分泌。
结论
我们发现高糖诱导大鼠小胶质细胞中 TNFα和 MCP-1 的分泌及其 mRNA 表达，这种作用是通过 ROS 和 NF-κB 途径介导的。
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