葡萄籽原花青素低聚体抑制A1型星形胶质细胞极化机制

Mechanism of grape seed proanthocyanidin oligomers inhibiting polarization of type A1 astrocytes

目的星形胶质细胞(astrocytes,AS)是脑内最丰富的神经胶质细胞,可对中枢神经系统(central nervous system,CNS)损伤迅速作出反应,极化为不同的表型。葡萄籽原花青素低聚体(grape seed proanthocyanidins,GSPs)可抑制CPZ小鼠髓鞘脱失,并致病灶区AS富集,所以本研究探索GSPs靶向AS的作用机制。方法以体外TNF-α、IL-1α和C1q诱导的A1型AS模型为研究对象,采用RT-PCR、ELISA和Western blot等方法检测GSPs对AS的表型及其分泌的细胞因子的影响,并对其机制进行初步探讨。结果GSPs减少A1型AS的标记C3d和C1q的表达,并抑制JNK的磷酸化。而且,与模型组相比,GSPs可明显抑制促炎因子IL-6、IL-1α、IL-17和H 2O 2的释放,促进抗炎因子TGF-β和神经营养因子CNTF的分泌。结论GSPs可抑制AS向A1型极化,改善炎性微环境,其机制与抑制JNK的磷酸化有关。

Aim To explore the mechanism of grape seed proanthocyanidins(GSPs)targeting astrocytes(AS),so as to regulate the phenotype and function of AS and maximize their neuroprotective effect.Methods The effects of GSPs on the phenotype,secretion of pro-inflammatory factors and neurotrophic factors of A1 AS induced by TNF-α,IL-1αand C1q were investigated by RT-PCR,Elisa and Western blot in vitro.And JNK phosphorylation was determined using Western blot.Results GSPs significantly reduced the expression of C3d and C1q of A1 AS markers and inhibited the phosphorylation of JNK.Moreover,compared with the model group,GSPs could significantly inhibit the release of pro-inflammatory cytokines IL-6,IL-1α,IL-17 and H 2O 2,and promote the secretion of anti-inflammatory cytokine TGF-βand neurotrophic factor CNTF.Conclusions GSPs can inhibit the polarization of AS to A1 and improve the inflammatory microenvironment,which are related to the inhibition of JNK phosphorylation.