原花青素抑制脂多糖激活神经小胶质细胞的机制

目的：研究原花青素抑制脂多糖（LPS）激活神经小胶质细胞的机制。方法：采用1.0 μg/mL LPS刺激神经小胶质细胞建立体外炎症模型，再用不同浓度（0.1、0.5、2.5、10.0 μg/mL）原花青素进行干预，四甲基噻唑蓝（MTT）法检测不同浓度原花青素对神经小胶质细胞的毒性，ELISA法检测炎症因子TNF-α、IL-1β、IL-6的表达，Western blot法检测TLR4、p38、p-p38蛋白的表达。结果：与对照组比较，1.0 μg/mL LPS组TNF-α、IL-1β、IL-6水平均显著升高（P < 0.05），TLR4和p-p38蛋白表达亦显著增加（P < 0.05）；给予不同浓度原花青素干预后，与1.0 μg/mL LPS组比较，炎性因子TNF-α、IL-1β、IL-6分泌水平均下降（P均 < 0.05），TLR4和p-p38蛋白表达水平均显著下调（P均 < 0.05）。结论：原花青素可能通过TLR4/p38 MAPK信号通路抑制脂多糖激活神经小胶质细胞。

Mechanism of proanthocyanidin-mediated inhibition of LPS-induced activation of microglial cells

OBJECTIVE: The present study was designed to investigate the possible mechanisms of proanthocyanidin-mediated inhibition in lipopolysaccharide (LPS)-induced activation of microglial BV2 cells. METHODS: An inflammation cell model was produced in BV2 cells which were treated with LPS (1.0 μg/mL). In addition,cells were treated with proanthocyanidins (0.1,0.5,2.5,10.0 μg/mL) prior to LPS exposure and MTT assay was used to detect the viability of BV2 cells. The level of inflammatory cytokines TNF-α,IL-1β and IL-6 were examined by ELISA method. TLR4 and p38,p-p38 MAPK protein expressions were examined by the Western blot analysis. RESULTS: Compared with the control group,LPS (1.0 μg/mL) significantly increased the expression of TLR4 and p-p38 protein as well as the release of inflammatory mediator TNF-α,IL-1β and IL-6 (P < 0.05). Proanthocyanidin significantly inhibited LPS-induced production of inflammatory mediators in a dose-dependent manner (P < 0.05). Moreover,PC significantly inhibited the phosphorylation of p38 and TLR4 expression (P < 0.05). CONCLUSION: Proanthocyanidin inhibited inflammatory mediator expression by suppressing TLR4 mediated p38 MAPK signaling pathways in LPS-stimulated BV2 cells.