Department of Basic Medicine, Changsha Health Vocational College, Changsha, 410600 Hunan, China.
Department of Neurology, Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine, Changsha, 410006 Hunan, China.
Mediators Inflamm. 2023 Feb 25;2023:9335166. doi: 10.1155/2023/9335166. eCollection 2023.
Ischemic stroke is a kind of central nervous disease characterized by high morbidity, high mortality, and high disability. Inflammation and autophagy play important roles in cerebral ischemia/reperfusion (CI/R) injury. The present study characterizes the effects of TLR4 activation on inflammation and autophagy in CI/R injury. An in vivo CI/R rat injury model and an in vitro hypoxia/reoxygenation (H/R) SH-SY5Y cell model were established. Brain infarction size, neurological function, cell apoptosis, inflammatory mediators' levels, and gene expression were measured. Infarction, neurological dysfunction, and neural cell apoptosis were induced in CI/R rats or in H/R-induced cells. The expression levels of NLRP3, TLR4, LC3, TNF-, interleukin-1 (IL-1), interleukin-6 (IL-6), and interleukin-18 (IL-18) clearly increased in I/R rats or in H/R-induced cells, while TLR4 knockdown significantly suppressed NLRP3, TLR4, LC3, TNF-, and interleukin-1/6/18 (IL-1/6/18) in H/R-induced cells, as well as cell apoptosis. These data indicate that TLR4 upregulation induced CI/R injury via stimulating NLRP3 inflammasome and autophagy. Therefore, TLR4, is a potential therapeutic target to improve management of ischemic stroke.
缺血性脑卒中是一种中枢神经系统疾病，具有发病率高、死亡率高和致残率高的特点。炎症和自噬在脑缺血/再灌注（CI/R）损伤中发挥重要作用。本研究探讨了 TLR4 激活对 CI/R 损伤中炎症和自噬的影响。建立了体内 CI/R 大鼠损伤模型和体外缺氧/复氧（H/R）SH-SY5Y 细胞模型。测量了脑梗死面积、神经功能、细胞凋亡、炎症介质水平和基因表达。在 CI/R 大鼠或 H/R 诱导的细胞中诱导了梗死、神经功能障碍和神经细胞凋亡。NLRP3、TLR4、LC3、TNF-、白细胞介素-1（IL-1）、白细胞介素-6（IL-6）和白细胞介素-18（IL-18）的表达水平在 I/R 大鼠或 H/R 诱导的细胞中明显增加，而 TLR4 敲低显著抑制了 H/R 诱导的细胞中 NLRP3、TLR4、LC3、TNF-和白细胞介素 1/6/18（IL-1/6/18），以及细胞凋亡。这些数据表明，TLR4 的上调通过刺激 NLRP3 炎症小体和自噬诱导 CI/R 损伤。因此，TLR4 可能成为改善缺血性脑卒中治疗的潜在靶点。
