Rodríguez-Cortés Yesica María, Ramírez-Carreto Ricardo Jair, Rodríguez-Barrena Julia Isabel, Salazar-Castro Marelly, Chavarría Anahí
Facultad de Medicina, Unidad de Medicina Experimental "Ruy Pérez Tamayo", Universidad Nacional Autónoma de México, Mexico City, Mexico.
Programa de Doctorado en Ciencias Biomédicas, Univesidad Nacional Autónoma de México, Mexico City, Mexico.
Front Aging Neurosci. 2024 Nov 18;16:1484946. doi: 10.3389/fnagi.2024.1484946. eCollection 2024.
Obesity is associated with a systemic inflammatory state that contributes to neuroinflammation and increases the risk of stroke at an early age. Stroke is the third leading cause of death worldwide and the leading cause of permanent disability. This work aimed to assess whether obesity-induced neuroinflammation can be a prognostic stroke factor that can be improved with oral administration of silymarin, an anti-inflammatory and neuroprotective drug.
Male C57/Bl6 mice were used to establish an obesity model through a high-fat diet (HFD) for 12 weeks. Cerebral ischemia was performed with photothrombosis in the left motor cortex at the end of the diet. Following the induction of ischemia, silymarin (100 mg/kg) was administered orally for 14 days. Levels of pro-inflammatory (IL1β, TNFα, and MCP1) and anti-inflammatory markers (IL4, IL10), neurotrophic factors (IGF1, BDNF), and CX3CL1 were assessed in the cortex and striatum using ELISA.
Mice on the HFD gained significantly more weight than control subjects and exhibited altered glucose metabolism, which was improved after silymarin treatment. The survival rate was significantly lower in HFD mice (52.2%) compared to control mice (86%). Silymarin treatment improved survival in both ischemic groups (non-diet control: 95.7%, HFD: 78.3%). Silymarin raised cortical TNFα, IL4, IL10, IGF1, BDNF, and CX3CL1 levels in the HFD group with stroke, while the striatum did not present relevant differences.
Our findings suggest that silymarin improves glucose metabolism, possibly impacting post-stroke survival in obese mice. The increased levels of neurotrophic factors BDNF and IGF1, along with microglial regulatory factor CX3CL1, may contribute to the improved survival observed. These results indicate that silymarin could be a potential therapeutic option for managing neuroinflammation and enhancing post-stroke outcomes in obese individuals.
肥胖与全身炎症状态相关，这种炎症状态会导致神经炎症，并增加早年发生中风的风险。中风是全球第三大死因，也是永久性残疾的主要原因。这项研究旨在评估肥胖诱导的神经炎症是否可能是一种中风预后因素，以及口服水飞蓟素（一种抗炎和神经保护药物）是否可以改善这一因素。
雄性C57/Bl6小鼠通过高脂饮食（HFD）喂养12周以建立肥胖模型。在饮食结束时，通过光血栓形成法在左侧运动皮层诱导脑缺血。缺血诱导后，口服水飞蓟素（100mg/kg），持续14天。使用酶联免疫吸附测定法（ELISA）评估皮层和纹状体中促炎标志物（IL1β、TNFα和MCP1）、抗炎标志物（IL4、IL10）、神经营养因子（IGF1、BDNF）和CX3CL1的水平。
高脂饮食组小鼠的体重显著高于对照组，且出现了糖代谢改变，水飞蓟素治疗后有所改善。高脂饮食组小鼠的存活率（52.2%）显著低于对照组小鼠（86%）。水飞蓟素治疗提高了两组缺血小鼠的存活率（非饮食对照组：95.7%，高脂饮食组：78.3%）。在发生中风的高脂饮食组中，水飞蓟素提高了皮层TNFα、IL4、IL10、IGF1、BDNF和CX3CL1的水平，而纹状体未出现相关差异。
我们的研究结果表明，水飞蓟素可改善糖代谢，可能影响肥胖小鼠中风后的存活率。神经营养因子BDNF和IGF1水平的升高，以及小胶质细胞调节因子CX3CL1，可能有助于观察到的存活率提高。这些结果表明，水飞蓟素可能是治疗肥胖个体神经炎症和改善中风后预后的潜在治疗选择。
