Mu Qiong, Wang Likun, Hang Hang, Liu Chunfeng, Wu Guofeng
Department of Neurology, The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou, 215004 China; Emergency Department, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China.
Emergency Department, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China.
Neurosci Lett. 2017 Jun 9;651:159-164. doi: 10.1016/j.neulet.2017.04.038. Epub 2017 Apr 23.
To explore the protective role of rosiglitazone against secondary brain injury after cerebral hemorrhage, we investigated the effect of rosiglitazone pretreatment on thrombin-induced microglial phagocytosis and described the molecular mechanisms involved in this process.
Primary microglial cells were obtained from the brain tissue of newborn Sprague-Dawley rats and were randomly divided into four groups: the normal, thrombin stimulation, thrombin-treated plus rosiglitazone, and thrombin-rosiglitazone plus proliferator-activated receptor-gamma (PPARγ) antagonist groups. Microglial phagocytosis was measured using a laser scanning confocal microscope. The expression of PPARγ and cluster of differentiation 36 (CD36) in each group was detected via quantitative reverse transcription-PCR and western blot analysis.
The thrombin-treated plus rosiglitazone group showed a significant increase in phagocytic activity compared to the other groups (P<0.05), while the PPARγ antagonist group significantly reduced microglial phagocytosis compared to the thrombin-treated plus rosiglitazone and the normal group. Moreover, the expression of PPARγ and CD36 was considerably higher in the thrombin-treated plus rosiglitazone group than in the normal and the thrombin group. Nevertheless, the thrombin-rosiglitazone-PPARγ group expressed a lower level of PPARγ and CD36 compared to the thrombin-treated plus rosiglitazone group.
Rosiglitazone can increase thrombin-induced microglial phagocytosis, by a mechanism possibly involved in the increase of PPARγ and CD36 through the PPARγ pathway, which may provide a new option for cerebral hemorrhage treatment.
为探讨罗格列酮对脑出血后继发性脑损伤的保护作用，我们研究了罗格列酮预处理对凝血酶诱导的小胶质细胞吞噬作用的影响，并阐述了这一过程中涉及的分子机制。
从新生Sprague-Dawley大鼠的脑组织中获取原代小胶质细胞，并随机分为四组：正常组、凝血酶刺激组、凝血酶处理加罗格列酮组和凝血酶-罗格列酮加增殖激活受体-γ（PPARγ）拮抗剂组。使用激光扫描共聚焦显微镜测量小胶质细胞的吞噬作用。通过定量逆转录聚合酶链反应和蛋白质免疫印迹分析检测每组中PPARγ和分化簇36（CD36）的表达。
与其他组相比，凝血酶处理加罗格列酮组的吞噬活性显著增加（P<0.05），而PPARγ拮抗剂组与凝血酶处理加罗格列酮组和正常组相比，显著降低了小胶质细胞的吞噬作用。此外，凝血酶处理加罗格列酮组中PPARγ和CD36的表达明显高于正常组和凝血酶组。然而，与凝血酶处理加罗格列酮组相比，凝血酶-罗格列酮-PPARγ组中PPARγ和CD36的表达水平较低。
罗格列酮可增加凝血酶诱导的小胶质细胞吞噬作用，其机制可能是通过PPARγ途径增加PPARγ和CD36，这可能为脑出血治疗提供新的选择。
