First Clinical Medical College, Guizhou University of Traditional Chinese Medicine, Guiyang 550001, Guizhou, China.
Jinyang Hospital Affiliated to Guizhou Medical University, Guiyang 550081, Guizhou, China.
Brain Res. 2024 Apr 15;1829:148845. doi: 10.1016/j.brainres.2024.148845. Epub 2024 Mar 5.
Formononetin has been demonstrated to protect against cerebral ischemia-reperfusion injury, however its mechanism has to be further researched. This study examined the effect of formononetin on cerebral ischemia-reperfusion injury in rats using the PARP-1/PARG/Iduna signaling pathway. In male SD rats, a model of cerebral ischemia-reperfusion injury was developed. Animals were randomly assigned to one of eight groups: Sham operation, Sham operation + formononetin, MCAO, MCAO + formononetin, PARP inhibitor (PJ34) + MCAO, formononetin + PJ34 + MCAO, PARG inhibitor (Ethacridine lactate) + MCAO, and ethacridine lactate + formononetin. The neurological deficit test, TTC staining, HE staining, Nissl staining, TUNEL staining, and western blotting were utilized to assess formononetin's protective effects in MCAO rats. The data show that formononetin can effectively alleviate neurological dysfunction and pathological changes in brain tissue in rats with cerebral ischemia-reperfusion injury, reduce the area of cerebral infarction and neuronal apoptosis, decrease the protein levels of PARP-1, PARG, Caspase-3, P53, and AIF in brain tissue, and increase the protein levels of Iduna and p-AKT. As a result, we concluded that formononetin improves brain ischemia-reperfusion injury in rats by modulating the PARP-1/PARG/Iduna signaling pathway.
芒柄花素已被证明可预防脑缺血再灌注损伤，但仍需进一步研究其作用机制。本研究通过 PARP-1/PARG/Iduna 信号通路探讨芒柄花素对大鼠脑缺血再灌注损伤的影响。雄性 SD 大鼠构建脑缺血再灌注损伤模型，将动物随机分为 8 组：假手术组、假手术+芒柄花素组、大脑中动脉阻塞（MCAO）组、MCAO+芒柄花素组、PARP 抑制剂（PJ34）+MCAO 组、芒柄花素+PJ34+MCAO 组、PARG 抑制剂（Ethacridine lactate）+MCAO 组和 Ethacridine lactate+芒柄花素组。采用神经功能缺损评分、TTC 染色、HE 染色、尼氏染色、TUNEL 染色和 Western blot 检测芒柄花素对 MCAO 大鼠的保护作用。结果表明，芒柄花素可有效减轻脑缺血再灌注损伤大鼠的神经功能障碍和脑组织病理改变，减少脑梗死面积和神经元凋亡，降低脑组织中 PARP-1、PARG、Caspase-3、P53 和 AIF 的蛋白水平，增加 Iduna 和 p-AKT 的蛋白水平。综上，芒柄花素通过调节 PARP-1/PARG/Iduna 信号通路改善大鼠脑缺血再灌注损伤。
