| 摘要: |
| 目的 探讨替罗非班能否通过沉默信息调节因子2相关酶1（SIRT1）/血管内皮生长因子（VEGF）信号通路减轻急性脑梗死（ACI）大鼠神经元损伤。方法 将75只SD大鼠随机分为假手术组、模型组、替罗非班（60 μg/kg）组、SIRT1抑制剂（5 mg/kg SIRT1特异性抑制剂EX-527）组、替罗非班＋SIRT1抑制剂组，每组15只。除假手术组外，其他4组大鼠构建ACI模型。对各组大鼠进行神经功能评分；采用氯化三苯基四氮唑染色检测大鼠脑梗死体积百分数；采用硫代巴比妥酸法检测大鼠血清丙二醛水平，采用比色法检测血清谷胱甘肽过氧化物酶（GSH-Px）水平，采用微板法检测血清超氧化物歧化酶（SOD）水平；采用H-E染色检测大鼠脑组织病理变化；采用TUNEL染色检测大鼠神经元凋亡水平；采用蛋白质印迹法检测大鼠海马组织中SIRT1、VEGF蛋白的表达。结果 与假手术组比较，模型组大鼠脑组织海马区病理损伤严重，神经功能评分、脑梗死体积百分数、血清丙二醛水平、神经元凋亡率均较高（P均＜0.05），血清GSH-Px、SOD水平及海马组织中SIRT1、VEGF蛋白表达水平均降低（P均＜0.05）。与模型组比较，替罗非班组、替罗非班＋SIRT1抑制剂组大鼠脑组织海马区病理损伤减轻，神经功能评分、脑梗死体积百分数、血清丙二醛水平、神经元凋亡率均降低（P均＜0.05），血清GSH-Px、SOD水平及海马组织中SIRT1、VEGF蛋白表达水平均升高（P均＜0.05）；而SIRT1抑制剂组大鼠相应指标变化呈相反趋势（P均＜0.05）。结论 替罗非班可能通过激活SIRT1/VEGF信号通路抑制氧化应激和神经元凋亡，进而减轻ACI大鼠的神经元损伤。 |
| 关键词: 替罗非班 急性脑梗死 沉默信息调节因子2相关酶1 血管内皮生长因子 神经元损伤 细胞凋亡 氧化性应激 |
| DOI：10.16781/j.CN31-2187/R.20220615 |
| 投稿时间：2022-07-01修订日期：2022-11-14 |
| 基金项目:河南省医学科技攻关计划联合共建项目（LHGJ20200763）. |
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| Tirofiban alleviating neuronal injury in acute cerebral infarction rats by regulating SIRT1/VEGF signaling pathway |
| WANG Wen-wen1,SHAO Yan-jiang2,MA Qi1,ZHANG Xin-le1,YANG Gai-qing3,XU Guo-wei3* |
(1. Department of Pharmacy, The 7th People's Hospital of Zhengzhou, Zhengzhou 450016, Henan, China;
2. Department of Pharmaceutical Analysis, School of Pharmacy, Zhengzhou University, Zhengzhou 450000, Henan, China;
3. Department of Neurology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450001, Henan, China
*Corresponding author) |
| Abstract: |
| Objective To investigate the effects of tirofiban on neuron injury in acute cerebral infarction (ACI) rats through silent information regulator factor 2-related enzyme 1 (SIRT1)/vascular endothelial growth factor (VEGF) signaling pathway. Methods Seventy-five SD rats were randomly divided into sham group, model group, tirofiban (60 μg/kg) group, SIRT1 inhibitor (5 mg/kg SIRT1 specific inhibitor EX-527) group, and tirofiban＋SIRT1 inhibitor group, with 15 rats in each group. Except for the sham group, ACI models were constructed in the other 4 groups. The rats in each group were scored for neurological function. Triphenyl tetrazolium chloride staining was used to analyze the cerebral infarction volume percentage of rats. The serum malondialdehyde level was measured by thiobarbituric acid method, glutathione peroxidase (GSH-Px) level was detected by colorimetry, and superoxide dismutase (SOD) level was detected by microplate test. Hematoxylin-eosin staining was used to detect the pathological changes of rat brain tissue. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay was used to detect the apoptosis of rat neurons. Western blotting was used to detect the expression of SIRT1 and VEGF proteins in the hippocampal tissue of rats. Results Compared with the sham group, the pathological damage of the hippocampus was more serious in the model group, the neurological function score, cerebral infarction volume percentage, serum malondialdehyde level and neuronal cell apoptosis rate were significantly increased (all P＜0.05), and the levels of serum GSH-Px and SOD and the expression levels of SIRT1 and VEGF proteins in the hippocampal tissue were significantly decreased (all P＜0.05). Compared with the model group, the pathological damage of the hippocampus was decreased in the tirofiban group and tirofiban＋SIRT1 inhibitor group, the neurological function scores, cerebral infarction volume percentage, serum malondialdehyde levels and neuronal cell apoptosis rates were significantly decreased (all P＜0.05), and the levels of serum GSH-Px and SOD and the expression levels of SIRT1 and VEGF proteins in the hippocampal tissue were significantly increased (all P＜0.05); however, the corresponding indexes of the rats in the SIRT1 inhibitor group showed an opposite trend (all P＜0.05). Conclusion Tirofiban may inhibit oxidative stress and neuron apoptosis by activating SIRT1/VEGF signaling pathway, thus alleviating neuron injury in ACI rats. |
| Key words: tirofiban acute cerebral infarction silent information regulator factor 2-related enzyme 1 vascular endothelial growth factor neuron injury apoptosis oxidative stress |
