Parthenolide抑制脑缺血后神经炎症并促进纹状体内神经发生

Parthenolide inhibits neuroinflammation and promotes neurogenesis in the ischemic striatum following transient middle cerebral artery occlusion in the adult rat brain

目的:检测Parthenolide是否抑制脑缺血诱发的神经炎症及其分子机制。方法:MCAO大鼠腹腔注射parthenol-ide(500μg/kg),行BrdU、BrdU-DCX、BrdU-Tuj-1、BrdU-MAP-2、BrdU-GFAP免疫组化和Western blot检测缺血侧纹状体组织TNF-α表达水平。结果:脑缺血增加缺血侧纹状体内TNF-α表达水平,Parthenolide抑制TNF-α的表达并促进缺血侧纹状体内新生细胞的增殖。给予Parthenolide在脑缺血后3 d、7 d或28 d增加BrdU+-DCX+,BrdU+-Tuj-1+,and Br-dU+-MAP-2+阳性细胞数,同时减少BrdU+-GFAP+阳性细胞数。结论:Parthenolide抑制脑缺血诱发的神经炎症,促进非神经发生区-纹状体内神经发生。尚需在此模型上进一步阐明其分子作用机制。

AIM： The objective of this study was to test the hypothesis that parthenolide suppresses ischemia-induced neuroinflammation in the MCAO model of adult rat. METHODS： MCAO rats were treated i. p. with parthenolide （500μg/kg）. Brain sections were analyzed for BrdU, BrdU- DCX, BrdU-Tuj-1, BrdU-MAP-2 and BrdU-GFAP staining. Total protein was extracted from ischemic striatum, and Western blot was used to determine TNF-α expression. RESULTS： Cerebral ischemia increases expression of TNF-α in the ischemic striatum. Parthenolide suppressed the expression of TNF-α and enhances the proliferation of newborn cells in the ischemic striatum. The cell number of Br- dU ＋-DCx ＋, BrdU ＋-Tuj-1 ＋, and BrdU ＋-MAP-2 ＋ is increased in the ischemic striatum after parthenolide treatment at 3 d, 7 d or 2.8 d after MCAO. Furthermore, parthenolide depressed the cell number of BrdU ＋ -GFAP ＋ in the ischemic striatum at 3 d, 7 d and 28 d after MCAO. CONCLUSION： Parthenolide inhibits neuroinflammation induced by cerebral ischemia and promotes neurogenesis in the ischemic striatum. Further study of the effects of parthenolide on inflammatory gene expression using model animal systems as described here are critical to elucidating their mechanisms of action.