Department of Neurosurgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
Int J Mol Med. 2022 Aug;50(2). doi: 10.3892/ijmm.2022.5164. Epub 2022 Jun 28.
The present study aimed to investigate the effects of long non‑coding (lncRNA) dihydrofolate reductase‑like 1 (DHFRL1‑4) on cerebral ischemia/reperfusion (I/R)‑induced injury. For this purpose, mice injected with lentivirus with small interfering RNA targeting DHFRL1‑4 or negative control siRNA were used to construct models of cerebral I/R injury. Following the establishment of the model, the infarct size, neurological deficit score, apoptosis and the expression levels of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), Wnt family member 3a (Wnt3a), glycogen synthase kinase‑3β (GSK‑3β) and phosphorylated GSK‑3β were assessed. The expression of DHFRL1‑4 was significantly upregulated in the I/R model. In the control and sham groups, the boundaries between the cortex and gray matter were clear, and no edema or necrosis were observed. The nerve cells were arranged orderly and evenly, and the cell membranes were intact with visible nucleus and nucleolus. In the model group however, the nerve fibers were slightly necrotic and swollen, and the number of nerve cells was reduced. In the mice injected with si‑DHFRL1‑4 lentivirus, the brain tissues exhibited less liquefaction and degeneration, as well as less edema. Compared with the control and sham groups, the model group had a significantly larger infarct area, a higher apoptotic rate, higher bFGF, VEGF, Wnt3a and GSK‑3β expression levels and a greater neurological deficit score. However, the mice injected with si‑DHFRL1‑4 lentivirus exhibited a significantly reduced infarct area, a lower apoptotic rate, lower Wnt3a and GSK‑3β expression levels, a lower neurological deficit score, and significantly upregulated bFGF and VEGF levels.
本研究旨在探讨长链非编码 RNA（lncRNA）二氢叶酸还原酶样 1（DHFRL1-4）对脑缺血/再灌注（I/R）损伤的影响。为此，使用靶向 DHFRL1-4 的小干扰 RNA 或阴性对照 siRNA 的慢病毒注射小鼠构建脑 I/R 损伤模型。模型建立后，评估梗死面积、神经功能缺损评分、凋亡以及碱性成纤维细胞生长因子（bFGF）、血管内皮生长因子（VEGF）、Wnt 家族成员 3a（Wnt3a）、糖原合成酶激酶-3β（GSK-3β）和磷酸化 GSK-3β 的表达水平。结果显示，I/R 模型中 DHFRL1-4 的表达显著上调。在对照组和假手术组中，皮质和灰质之间的边界清晰，未见水肿或坏死。神经细胞排列整齐均匀，细胞膜完整，可见细胞核和核仁。然而，在模型组中，神经纤维轻微坏死和肿胀，神经细胞数量减少。在注射 si-DHFRL1-4 慢病毒的小鼠中，脑组织液化和变性程度较轻，水肿程度较轻。与对照组和假手术组相比，模型组的梗死面积明显增大，凋亡率明显升高，bFGF、VEGF、Wnt3a 和 GSK-3β 的表达水平显著升高，神经功能缺损评分显著升高。然而，注射 si-DHFRL1-4 慢病毒的小鼠梗死面积明显减小，凋亡率降低，Wnt3a 和 GSK-3β 的表达水平降低，神经功能缺损评分降低，bFGF 和 VEGF 的表达水平显著升高。
