• Jianjiao Qi, Bin Han, Zhiyuan Wang, Lihong Jing, Xintao Tian, and Jinping Sun.
• Department of Emergency Medicine, the Affiliated Hospital of Qingdao University, Qingdao 266000, China.
• Neuroscience. 2024 Jan 26; 537: 213121-31.

Background And PurposeApoptosis is involved in the occurrence and development of acute ischemic stroke (AIS). This study aimed to assess whether Chuanzhitongluo (CZTL), a multi-target and multi-pathway compound preparation, plays a neuroprotective role in AIS by modulating neuronal apoptosis via the PI3K/AKT signaling pathway.MethodsA mouse model of AIS was established by photochemical processes. Cerebral infarction volume was measured by 2% staining with 2, 3, and 5-triphenyl tetrazole chloride (TTC). Neuron apoptosis was assessed by TUNEL staining. Apoptosis RNA arrays were used to detect changes in apoptosis-related gene expression profiles. Western blotting was used to detect proteins involved in the PI3K/AKT signaling pathway.ResultsThe study demonstrated that CZTL could potentially mitigate neuronal apoptosis in AIS mice. This appears to be achieved via the up-regulation of certain genes such as BCL-2, Birc6, and others, coupled with the down-regulation of genes like BAX, Bid, and Casp3. Further validation revealed that CZTL could enhance the expression of BCL-2 and reduce the expression of Cleaved Caspase-3 and BAX at both the gene and protein levels. The study also found that CZTL can enhance the phosphorylation level of the PI3K/AKT signaling pathway. In contrast to these findings, the PI3K inhibitor LY294002 notably amplified neuronal apoptosis in AIS mice.ConclusionsThese findings imply that CZTL's ability to inhibit neuronal apoptosis may be linked to the activation of AIS's PI3K/AKT signaling pathway.Copyright © 2023 IBRO. Published by Elsevier Inc. All rights reserved.

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