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Abstract：
Previous studies have shown that scutellarin inhibits the excessive activation of microglia, reduces neuronal apoptosis, and exerts neuroprotective effects. However, whether scutellarin regulates activated microglia-mediated neuronal apoptosis and its mechanisms remains unclear. This study aimed to investigate whether scutellarin can attenuate PC12 cell apoptosis induced by activated microglia via the JAK2/STAT3 signalling pathway. Microglia were cultured in oxygen-glucose deprivation (OGD) medium, which acted as a conditioning medium (CM) to activate PC12 cells, to investigate the expression of apoptosis and JAK2/STAT3 signalling-related proteins. We observed that PC12 cells apoptosis in CM was significantly increased, the expression and fluorescence intensity of the pro-apoptotic protein Bax and apoptosis-related protein cleaved caspase-3 were increased, and expression of the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) was decreased. Phosphorylation levels and fluorescence intensity of the JAK2/STAT3 signalling pathway-related proteins JAK2 and STAT3 decreased. After treatment with scutellarin, PC12 cells apoptosis as well as cleaved caspase-3 and Bax protein expression and fluorescence intensity decreased. The expression and fluorescence intensity of Bcl-2, phosphorylated JAK2, and STAT3 increased. AG490, a specific inhibitor of the JAK2/STAT3 signalling pathway, was used. Our findings suggest that AG490 attenuates the effects of scutellarin. Our study revealed that scutellarin inhibited OGD-activated microglia-mediated PC12 cells apoptosis which was regulated via the JAK2/STAT3 signalling pathway.
摘要：
以前的研究表明，灯盏乙素抑制小胶质细胞的过度激活，减少神经元凋亡，并发挥神经保护作用。然而,灯盏乙素是否调节活化的小胶质细胞介导的神经元凋亡及其机制尚不清楚。本研究旨在探讨灯盏乙素能否通过JAK2/STAT3信号通路抑制活化小胶质细胞诱导的PC12细胞凋亡。小胶质细胞在氧-葡萄糖剥夺（OGD）培养基中培养，它充当了激活PC12细胞的调节介质（CM），探讨细胞凋亡和JAK2/STAT3信号相关蛋白的表达。我们观察到PC12细胞凋亡在CM中显著增加，促凋亡蛋白Bax和凋亡相关蛋白caspase-3的表达和荧光强度增加，抗凋亡蛋白B细胞淋巴瘤-2（Bcl-2）的表达降低。JAK2/STAT3信号通路相关蛋白JAK2和STAT3的磷酸化水平和荧光强度降低。用灯盏乙素治疗后，PC12细胞凋亡以及caspase-3和Bax蛋白表达和荧光强度降低。Bcl-2、磷酸化JAK2和STAT3的表达和荧光强度增加。AG490是JAK2/STAT3信号通路的特异性抑制剂，被使用。我们的发现表明AG490减弱了灯盏乙素的作用。我们的研究表明，灯盏乙素抑制OGD激活的小胶质细胞介导的PC12细胞凋亡，该凋亡是通过JAK2/STAT3信号通路调节的。
