Apelin-13对大鼠脑缺血-再灌注损伤的保护作用

摘要: 目的 观察 Apelin-13 对大鼠脑缺血-再灌注损伤（CIRI）的保护作用并探讨其机制。方法 50 只 SD 雄性大鼠随机分为假手术组、 CIRI 模型组及低剂量(0.1 μg/kg)、 中剂量(1.0 μg/kg)和高剂量(10.0 μg/kg) Apelin-13 处理组。线栓法建立大鼠脑 CIRI 模型， 在缺血 2 h 后再灌注 72 h， Apelin-13 处理组于再灌注前 30 min 侧脑室注射 Apelin-13。对各组大鼠神经功能进行评分， TTC 染色观察并计算脑梗死体积百分比， Western blot 检测损伤侧大脑皮质中内质网应激标志蛋白葡萄糖调节蛋白 78 （GRP78） 和 C/EBP 同源蛋白 （CHOP） 的表达。结果 与假手术组比较， CIRI 模型组大鼠神经功能评分显著增加 （P < 0.05）， 脑梗死体积百分比达到 （47.63 ± 5.81） %； 损伤侧大脑皮质中 GRP78 和 CHOP 的表达量显著升高（均 P < 0.05）。与 CIRI 模型组相比， 低剂量组差异无统计学意义（P > 0.05）； 中剂量和高剂量 Apelin-13 处理组大鼠神经功能缺损明显改善， 肌力明显增强， 脑梗死体积百分比显著降低， 损伤侧大脑皮质中 GRP78 和 CHOP 的表达显著降低（均 P < 0.05）。结论 Apelin-13 对大鼠 CIRI 有保护作用， 其机制可能与抑制内质网应激有关。

Apelin-13 protects the cerebral ischemia-reperfusion injury in rats

Abstract: Objective To observe the protective effect of Apelin- 13 on the cerebral ischemia- reperfusion injury (CIRI), and to explore the possible mechanism in rat model. Methods Fifty male SD rats were randomly divided into five groups: sham group, CIRI model group and Apelin-13 (0.1, 1.0 and 10.0 μg/kg) treatment groups. The model of CIRI was es⁃ tablished by filament. After 2 h ischemia, the focal middle cerebral artery was followed by 72 h reperfusion. Apelin-13 was administrated by intracerebroventricular injection 30 minutes before reperfusion. The score of neural function was estimated in different time points. The 2,3,5- triphenyl tetrazolium chloride (TTC) dye was used to calculate the volume and percent⁃ age of cerebral infarction. The endoplasmic reticulum stress (ERS) protein markers including glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP) in cerebral cortex were measured by Western blot assay. Results Compared with the sham group, the score of neural function was significantly increased, the infarct rate was reached(47.63 ± 5.81)% and the protein expressions of GRP78 and CHOP were significantly up-regulated in CIRI mod⁃ el group (P<0.05). There were no significant differences in these data between the CIRI model group and 0.1 μg/kg Apelin- 13 treatment group (P>0.05). Compared with the CIRI group, the neural function defect was significantly improved, the mus⁃ cle strength was significantly enhanced and the infarct rate was significantly decreased, and the protein expressions of GRP78 and CHOP were significantly down-regulated in the 1.0 and 10.0 μg/kg Apelin-13 treatment groups (P<0.05). Con⁃ clusion Apelin-13 protects the cerebral ischemia-reperfusion injury in rat model, which may be related with the inhibition of endoplasmic reticulum stress.