Anhui Academy of Medical Sciences, Hefei, Anhui 230061, China.
Anhui Academy of Medical Sciences, Hefei, Anhui 230061, China.
Eur J Pharmacol. 2017 Jul 15;807:127-137. doi: 10.1016/j.ejphar.2017.04.002. Epub 2017 Apr 5.
Anfibatide (ANF) is a GPIb antagonist derived from the protein complex agglucetin. Previous studies have showed that it has protective effect on cerebral ischemia/reperfusion injury, the mechanism of which is still unclear, however. The present study was designed to investigate the protective effect of ANF on cerebral I/R injury in rats and the possible mechanisms. Focal cerebral ischemia was induced by 90min of transient middle cerebral artery occlusion (MCAO). ANF (1, 2, 4μg/kg) was achieved by intravenous injection after 120min of MCAO followed by 1h, 24h ,48h and 72h reperfusion. Neurological deficit, infarct volume, histopathology, neuronal apoptosis, NeuN and the expression of TLR4, total and phosphorylated c-Jun NH-terminal kinase (JNK/p-JNK), Bcl-2, Bax, caspase-3, NF-κB protein in rat brain, the levels of IL-1β, IL-6 and TNF-α in serum were evaluated 72h after reperfusion. ANF could significantly decrease neurological score, reduce the infarct volumes, ameliorate the histopathological alteration, attenuate the neuronal apoptosis and increase the fluorescence density of NeuN in the rat brain. Furthermore, ANF could obviously decrease the expression of TLR4, p-JNK, caspase-3, NF-κB , relative ratio of Bax/Bcl-2 in brain and the levels of IL-1β, IL-6 and TNF-α in serum. The results indicate that ANF has protective effect against cerebral I/R injury in rats and the underlying mechanism may be associated with the suppression of apoptosis through inhibiting TLR4/JNK/caspase-3 signaling pathway.
氨己烯酸（ANF）是一种从蛋白复合物聚集素衍生而来的 GPIb 拮抗剂。先前的研究表明，它对脑缺血/再灌注损伤具有保护作用，但具体机制尚不清楚。本研究旨在探讨 ANF 对大鼠脑 I/R 损伤的保护作用及其可能的机制。采用 90min 短暂性大脑中动脉闭塞（MCAO）诱导局灶性脑缺血。MCAO 后 120min 给予 ANF（1、2、4μg/kg）静脉注射，再灌注 1h、24h、48h 和 72h。再灌注 72h 后评估大鼠神经功能缺损、梗死体积、组织病理学、神经元凋亡、NeuN 及 TLR4、总及磷酸化 c-Jun NH2-末端激酶（JNK/p-JNK）、Bcl-2、Bax、caspase-3、核因子-κB（NF-κB）蛋白表达、血清中白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）水平。ANF 可显著降低神经功能评分，减少梗死体积，改善组织病理学改变，减轻神经元凋亡，增加大鼠脑组织中 NeuN 的荧光密度。此外，ANF 可明显降低脑内 TLR4、p-JNK、caspase-3、NF-κB、Bax/Bcl-2 相对比值及血清中 IL-1β、IL-6 和 TNF-α水平。结果表明，ANF 对大鼠脑 I/R 损伤具有保护作用，其作用机制可能与抑制 TLR4/JNK/caspase-3 信号通路相关。
