GM130 沉默可能通过下调 PD-L1 表达加重实验性脑出血后血脑屏障损伤并影响小胶质细胞极化。
GM130-silencing may aggravate blood-brain barrier damage and affect microglia polarization by down-regulating PD-L1 expression after experimental intracerebral hemorrhage.
机构信息
Department of Neurology, Second Xiangya Hospital, Central South University, No. 139, Renmin Middle Road, Changsha, Hunan, China.
Clinical Medical Research Center for Stroke Prevention and Treatment of Hunan Province, Department of Neurology, Second Xiangya Hospital, Central South University, Changsha, China.
出版信息
Mol Biol Rep. 2024 Aug 19;51(1):919. doi: 10.1007/s11033-024-09859-x.
BACKGROUND
In addition to primary injury, secondary injuries related to BBB disruption and immune-inflammatory response also play an important role in intracerebral hemorrhage (ICH). And the Golgi apparatus play an important role in the state of ICH.
METHODS
ICH model and GM130-silencing ICH model were established in SD rats. The Garcia score was used to score the neurological defects of the rats. Blood-brain barrier (BBB) integrity were assessed by amount of extravasated Evans blue, and tight junction proteins. The expression of PD-L1 and GM130were detected through Western-blot and the subtype of microglia was showing with Immunofluorescence staining.
RESULTS
Compared with the ICH group, GM130-silencing ICH rats got a worsened neurological deficit and enlarged volume of the hematoma. Evan's blue extravasation aggravated as well. The expression of GM130 in peri-hematoma tissue was further decreased, and the morphology and structure of the Golgi apparatus were further damaged. Meanwhile, the GM130 deficit resulted in decreased expression of PD-L1 and more polarization of microglia to the M1 subtype.
CONCLUSION
We demonstrate that GM130 could influence the integrity of BBB and plays a role in neuroinflammation via regulation of PD-L1 after ICH. The manipulation of GM130 might be a promising therapeutical target in ICH.
背景
除了原发性损伤外，与血脑屏障破坏和免疫炎症反应相关的继发性损伤在脑出血（ICH）中也起着重要作用。而高尔基器在 ICH 状态中起着重要作用。
方法
在 SD 大鼠中建立了 ICH 模型和 GM130 沉默 ICH 模型。采用 Garcia 评分对大鼠的神经缺损进行评分。通过伊文思蓝渗出量和紧密连接蛋白评估血脑屏障（BBB）的完整性。通过 Western blot 检测 PD-L1 和 GM130 的表达，通过免疫荧光染色显示小胶质细胞的亚型。
结果
与 ICH 组相比，GM130 沉默 ICH 大鼠的神经功能缺损加重，血肿体积增大。伊文思蓝渗出也加重了。GM130 在血肿周围组织中的表达进一步降低，高尔基器的形态和结构进一步受损。同时，GM130 的缺乏导致 PD-L1 的表达减少，小胶质细胞向 M1 亚型极化增加。
结论
我们证明 GM130 可以通过调节 PD-L1 在 ICH 后影响 BBB 的完整性并在神经炎症中发挥作用。GM130 的操纵可能是 ICH 的一种有前途的治疗靶点。
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