雷公藤甲素与雷公藤红素对小胶质细胞炎症反应的影响机制

Effects of triptolide and celastrol on the microglia inflammatory response

雷公藤甲素与雷公藤红素是雷公藤的主要生物活性成分,具有多种潜在的药理作用与毒性。神经炎症是各种神经退行性疾病的共同特征,小胶质细胞的激活是中枢神经系统神经炎症的主要组成部分。本文用雷公藤甲素与雷公藤红素处理小胶质细胞(HMO6),探究其对小胶质细胞增殖、细胞膜完整性的影响,以及雷公藤甲素对小胶质细胞M1、M2极化的影响。结果表明:与对照组相比,雷公藤红素(10^-4 mol/L)处理HMO6后,细胞增殖抑制率可高达(71.91±16.28)%(P<0.01,n=3),当浓度为10^-5 mol/L时,乳酸脱氢酶(LDH)释放量明显增加(8.58±1.56)%(P<0.01,n=4);与对照组相比,雷公藤甲素处理HMO6后,对细胞膜完整性无显著影响,但当浓度为10^-5 mol/L时,细胞增殖抑制率可高达(94.31±0.62)%(P<0.01,n=5),与脂多糖(LPS)组相比,雷公藤甲素浓度为10^-7 mol/L时人肿瘤坏死因子-α(TNF-α)释放量显著减少至(264.83±64.25)pg/mL(P<0.01,n=3),人白细胞介素-10(IL-10)释放量减少至(63.48±16.79)pg/mL(P<0.05,n=3)。

Triptolide and celastrol are the main bioactive components of Tripterygium wilfordii Hook F and have many potential pharmacological effects and toxicities.Neuroinflammation is a prominent feature shared by various neurodegenerative diseases.Microglial activation is the principal player in neuroinflammation of the central nervous system.In this work,triptolide and celastrol were used to treat microglia in order to investigate their effects on microglia proliferation and cell membrane integrity,and triptolide was used to treat microglia to investigate its effect on M1 and M2 polarization.The results showed that after treatment of HMO6 microglia with celastrol(with a concentration of 10^-4 mol/L),the inhibition of cell proliferation was higher than that of the control group,reaching(71.91±16.28)%(P<0.01,n=5),and the release of lactate dehydrogenase(LDH)(with a celastrol concentration of 10^-5 mol/L)was significantly increased by(8.58±1.56)%(P<0.01,n=4).Compared with the control group,after treatment of HMO6 microglia with triptolide,there was no significant effect on cell membrane integrity,but when the triptolide concentration is 10^-5 mol/L the cell proliferation inhibition was as high as(94.31±0.62)%(P<0.01,n=5).Compared with the lipopolysaccharide(LPS)group,when the triptolide concentration is 10^-7 mol/L the release of tumor necrosis factor-α(TNF-α)was significantly reduced to(264.83±64.25)pg/mL(P<0.01,n=3)and the release of interleukin-10(IL-10)was significantly decreased to(63.48±16.79)pg/mL(P<0.05,n=3).