PDF(Pubmed)
Abstract：
Intracerebral hemorrhage (ICH) comprises primary and secondary injuries, the latter of which induces increased inflammation and apoptosis and is more severe. Activating transcription factor 6 (ATF6) is a type-II transmembrane protein in the endoplasmic reticulum (ER). ATF6 target genes could improve ER homeostasis, which contributes to cryoprotection. Hence, we predict that ATF6 will have a protective effect on brain tissue after ICH.
The ICH rat model was generated through autologous blood injection into the right basal ganglia, the expression of ATF6 after ICH was determined by WB and IF. The expression of ATF6 was effectively controlled by means of intervention, and a series of measures was used to detect cell death, neuroinflammation, brain edema, blood-brain barrier and other indicators after ICH. Finally, the effects on long-term neural function of rats were measured by behavioral means.
ATF6 was significantly increased in the ICH-induced brain tissues. Further, ATF6 was found to modulate the expression of cystathionine γ-lyase (CTH) after ICH. Upregulation of ATF6 attenuated neuronal apoptosis and inflammation in ICH rats, along with mitigation of ICH-induced brain edema, blood-brain barrier deterioration, and cognitive behavior defects. Conversely, ATF6 genetic knockdown induced effects counter to those aforementioned.
This study thereby emphasizes the crucial role of ATF6 in secondary brain injury in response to ICH, indicating that ATF6 upregulation may potentially ameliorate ICH-induced secondary brain injury. Consequently, ATF6 could serve as a promising therapeutic target to alleviate clinical ICH-induced secondary brain injuries.
The ICH rat model was generated through autologous blood injection into the right basal ganglia, the expression of ATF6 after ICH was determined by WB and IF. The expression of ATF6 was effectively controlled by means of intervention, and a series of measures was used to detect cell death, neuroinflammation, brain edema, blood-brain barrier and other indicators after ICH. Finally, the effects on long-term neural function of rats were measured by behavioral means.
ATF6 was significantly increased in the ICH-induced brain tissues. Further, ATF6 was found to modulate the expression of cystathionine γ-lyase (CTH) after ICH. Upregulation of ATF6 attenuated neuronal apoptosis and inflammation in ICH rats, along with mitigation of ICH-induced brain edema, blood-brain barrier deterioration, and cognitive behavior defects. Conversely, ATF6 genetic knockdown induced effects counter to those aforementioned.
This study thereby emphasizes the crucial role of ATF6 in secondary brain injury in response to ICH, indicating that ATF6 upregulation may potentially ameliorate ICH-induced secondary brain injury. Consequently, ATF6 could serve as a promising therapeutic target to alleviate clinical ICH-induced secondary brain injuries.
摘要：
背景：脑出血（ICH）包括原发性和继发性损伤，后者诱导炎症和细胞凋亡增加，并且更严重。激活转录因子6（ATF6）是内质网（ER）中的II型跨膜蛋白。ATF6靶基因可以改善ER稳态，这有助于冷冻保护。因此，我们预测ATF6对脑出血后脑组织有保护作用。
方法：右侧基底节注射自体血制作ICH大鼠模型，通过WB和IF测定ICH后ATF6的表达。干预后ATF6的表达得到有效控制,一系列措施被用来检测细胞死亡，神经炎症，脑水肿,脑出血后血脑屏障等指标。最后,用行为学方法测定对大鼠远期神经功能的影响。
结果：ATF6在ICH诱导的脑组织中显著升高。Further,发现ATF6在ICH后调节胱硫醚γ-裂解酶（CTH）的表达。ATF6上调减轻ICH大鼠神经元凋亡和炎症反应,随着ICH引起的脑水肿的缓解，血脑屏障恶化，和认知行为缺陷。相反，ATF6基因敲低诱导的效果与上述效果相反。
结论：因此，本研究强调了ATF6在继发性脑损伤对ICH的反应中的关键作用，表明ATF6上调可能潜在地改善ICH诱导的继发性脑损伤。因此,ATF6可以作为减轻临床ICH引起的继发性脑损伤的有希望的治疗靶点。
方法：右侧基底节注射自体血制作ICH大鼠模型，通过WB和IF测定ICH后ATF6的表达。干预后ATF6的表达得到有效控制,一系列措施被用来检测细胞死亡，神经炎症，脑水肿,脑出血后血脑屏障等指标。最后,用行为学方法测定对大鼠远期神经功能的影响。
结果：ATF6在ICH诱导的脑组织中显著升高。Further,发现ATF6在ICH后调节胱硫醚γ-裂解酶（CTH）的表达。ATF6上调减轻ICH大鼠神经元凋亡和炎症反应,随着ICH引起的脑水肿的缓解，血脑屏障恶化，和认知行为缺陷。相反，ATF6基因敲低诱导的效果与上述效果相反。
结论：因此，本研究强调了ATF6在继发性脑损伤对ICH的反应中的关键作用，表明ATF6上调可能潜在地改善ICH诱导的继发性脑损伤。因此,ATF6可以作为减轻临床ICH引起的继发性脑损伤的有希望的治疗靶点。
