米诺环素对活化小胶质细胞的细胞毒性因子表达的影响

Effect of Minocycline on the Expression of Cytotoxic Factors in Activated Microglia

【目的】探讨米诺环素抑制小胶质细胞活化过程中细胞毒性因子表达的变化及意义。【方法】建立小胶质细胞体外培养模型，分为对照组、脂多糖（LPS）活化组和米诺环素干预组。在各时间点取细胞培养液，行ELISA方法检测TNF-α和IL-β蛋白含量，以及GriessReagent方法检测NO含量。【结果】①培养的小胶质细胞为圆形、折光性强的小细胞。经LPS活化后，胞体相对增大，呈巨噬细胞样，伴有多个细长的突起。②小胶质细胞产生的细胞毒性因子在对照组中也有少量存在。活化组细胞经LPS激活后TNF-α水平升高最早，其次为IL-1β，而N0最晚。干预组的TNF-α在各时间点均可见其含量较活化组显著下降；之后出现IL-1β的显著下降，而NO最晚出现。【结论】米诺环素可以抑制活化小胶质细胞的细胞毒性因子的产生。

[Objective] To explore the change of the expression of cytotoxic factors in activated process of microglia inhibited by minocycline. [Methods]The models of microglia in vitro was established and divided into control group, LPS-activated group and minocycline treated group. At all time points, cell culture fluid was obtained. Enzyme-linked immunosorbent assay（ELISA） method was used to detect the protein expression of tumor necrosis factor-alpha（TNF-α） and interleukin-1 beta（IL-1β）. The level of nitric oxide（NO） was measured by Griess reagent assay. [Results] The cultured microglial cells were small round with strong refraction. After activated by LPS, the cell bodies relatively increased with multiple slender prominences like macrophages. The expression of cytotoxic factors produced by mieroglia in control group was little. In activated group, the elevation of TNF-α in cells activated by LPS was the earliest, and that of IL- 1β was the second, and that of NO was the latest. Compared with LPS-activated group, the level of TNF-α in minocycline-treated group in all time points significantly decreased, and then IL-1β decreased, and finally NO decreased. [Conclusion]Minocycline may inhibit the production of cytotoxic factors in activated microglia.