ICU Department, Jiyang People's Hospital of Jinan, Jinan, China.
Yonsei Med J. 2022 Oct;63(10):956-965. doi: 10.3349/ymj.2022.0040.
Cerebral ischemia-reperfusion (IR) injury is a severe secondary injury induced by reperfusion after stroke. Didymin has been reported to have a protective effect on intracerebral hemorrhage. However, the underlying mechanism of didymin on regulating cerebral IR injury remains largely unknown.
A rat cerebral IR model and oxygen-glucose deprivation/reperfusion (OGD/R) model in PC12 cells were established. Hematoxylin and eosin (H&E) was used to detect the pathological changes in brain tissues, and TUNEL staining was performed to detect apoptosis of brain tissues. MTT and flow cytometry were used to measure the viability and apoptosis of PC12 cells. QRT-PCR and western blot were used to detect inflammation cytokines in PC12 cells. Western blot was used to measure the expression of PPAR-γ, RXRA, Bax, c-caspase-3, and Bcl-2.
Didymin pretreatment decreased apoptotic rates, reduced levels of Bax and c-caspase-3, and increased Bcl-2 level in vivo and in vitro. Additionally, didymin pretreatment increased viability and decreased the inflammation levels [interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and monocyte chemotactic protein (MCP)-1] of OGD/R treated PC12 cells. Moreover, didymin activated the peroxisome proliferator-activated receptors (PPAR) signaling pathway and increased the expression of PPAR-γ and RXRA in OGD/R treated PC12 cells. Inhibition of PPAR-γ eliminated the protective effect of didymin on OGD/R treated cells.
Didymin protected neuron cells against IR injury in vitro and in vivo by activation of the PPAR pathway. Didymin may be a candidate drug for IR treatment.
脑缺血再灌注（IR）损伤是中风后再灌注引起的严重继发性损伤。曾报道二氢杨梅素对脑出血有保护作用。然而，二氢杨梅素调节脑 IR 损伤的潜在机制在很大程度上尚不清楚。
建立大鼠脑 IR 模型和 PC12 细胞氧葡萄糖剥夺/再灌注（OGD/R）模型。苏木精和伊红（H&E）用于检测脑组织的病理变化，TUNEL 染色用于检测脑组织的细胞凋亡。MTT 和流式细胞术用于检测 PC12 细胞的活力和凋亡。QRT-PCR 和 Western blot 用于检测 PC12 细胞中的炎症细胞因子。Western blot 用于检测 PPAR-γ、RXRA、Bax、c-caspase-3 和 Bcl-2 的表达。
二氢杨梅素预处理降低了体内和体外的细胞凋亡率，降低了 Bax 和 c-caspase-3 的水平，并增加了 Bcl-2 的水平。此外，二氢杨梅素预处理增加了 OGD/R 处理的 PC12 细胞的活力，降低了炎症水平[白细胞介素（IL）-1β、IL-6、肿瘤坏死因子（TNF）-α 和单核细胞趋化蛋白（MCP）-1]。此外，二氢杨梅素激活过氧化物酶体增殖物激活受体（PPAR）信号通路，增加了 OGD/R 处理的 PC12 细胞中 PPAR-γ 和 RXRA 的表达。PPAR-γ 抑制剂消除了二氢杨梅素对 OGD/R 处理细胞的保护作用。
二氢杨梅素通过激活 PPAR 通路，在体外和体内保护神经元细胞免受 IR 损伤。二氢杨梅素可能是治疗 IR 的候选药物。
