基于cGMP - PKG/PKA信号通路探究奥扎格雷对ACI模型大鼠认知功能的干预机制

To investigate the intervention mechanism of Ozagrel on cognitive function of ACI rats based on cGMP-PKG/PKA signaling pathway

目的研究基于环磷酸鸟苷-蛋白激酶G(cGMP)-蛋白激酶G(PKG)/蛋白激酶A(PKA)信号通路探究奥扎格雷对急性脑梗死(ACI)模型大鼠认知功能的干预机制。方法选取清洁及健康的32只雄性大鼠,8只为正常组,剩余24只建立ACI模型,分为模型组、低剂量奥扎格雷组、高剂量奥扎格雷组,每组各8只。检测各组大鼠逃避潜伏期,穿越平台次数、平台停留时间、脑源性神经营养因子(BDNF)、神经生长因子(NGF)、cGMP、PKG、PKA水平,测量梗死面积,评估神经功能评分。结果与正常组大鼠相比,模型组、低剂量奥扎格雷组、高剂量奥扎格雷组逃避潜伏期较多,穿越平台次数、平台停留时间少,梗死面积、神经功能评分较高,BDNF、NGF水平较低(P<0.05);与模型组大鼠相比,低剂量奥扎格雷组、高剂量奥扎格雷组大鼠逃避潜伏期较少,穿越平台次数、平台停留时间较多,梗死面积、神经功能评分较低,以及BDNF、NGF水平较高(P<0.05)与正常组大鼠相比,模型组、低剂量奥扎格雷组、高剂量奥扎格雷组大鼠cGMP、PKG水平较高,PKA水平较低(P<0.05);与模型组大鼠相比,低剂量奥扎格雷组、高剂量奥扎格雷组大鼠cGMP、PKG水平较低,PKA水平较高(P<0.05)。高剂量奥扎格雷组表现最为明显。结论高剂量奥扎格雷通过调控cGMP-PKG/PKA信号通路蛋白水平及血清中BDNF、NGF水平,来改善大鼠的认知功能。

Objective To study the cyclic guanosine monophosphate protein kinase G(cGMP)-protein kinase G(PKG)/protein kinase A(PKA) signaling pathway in the intervention mechanism of Ozagrel on cognitive function in rats with acute cerebral infarction(ACI). Methods Thirty-two male rats were selected. And 8 were assigned into normal group, while the other 24 received ACI modeling. The ACI rats were divided into model group, low and high dose ozagre groups. The escape latency, the number of times of crossing the platform, the residence time in the platform, the brain-derived neurotrophic factor(BDNF), nerve growth factor(NGF), cGMP, PKG, and PKA levels were measured in each group. The infarct area was measured and the neurological function score was evaluated. Results Compared with the normal group, the rats in model group, low-dose and high-dose Ozagrel group had more escape latency, less times of crossing platform, shorter platform stay time, higher score of infarct area and nerve function, and lower BDNF and NGF(P<0.05). Compared with the model group, the rats in the low-and high-dose Ozagrel group had less escape latency, more times of crossing platform, longer time of stay, lower score of infarct area and nerve function, and higher levels of BDNF and NGF(P<0.05). Compared with the normal group, the cGMP and PKG levels of the model group, the low-and high-dose Ozagrel group were significantly higher and the PKA levels were significantly lower(P<0.05). Compared with the model group, the levels of cGMP and PKG in the low-and high-dose Ozagrel group were significantly lower and PKA levels were significantly higher(P<0.05). The high-dose Ozagrel group showed the most obvious. Conclusion High dose Ozagrel can improve the cognitive function of rats by regulating cGMP PKG/PKA signaling pathway protein levels and serum BDNF and NGF levels.