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目的:研究γ-羟基丁酸受体(GHBR)在大鼠局灶性脑缺血再灌注(I/R)损伤中的作用及其作用机制。方法:采用改良的Longa线栓法缺血2 h/再灌2 h建立I/R模型。分别于缺血前30 min和再灌前经侧脑室(icv)给予药物;5分制评分法评价大鼠神经功能。再灌注24 h后,放免法测定大鼠脑缺血皮层神经元的cAMP含量;Western-blot测定蛋白激酶A(PKA)四聚体水平。结果:I/R组大鼠行为学评分明显高于假手术组;NCS-356 640组的行为学评分则明显低于I/R组。I/R组大鼠脑缺血区皮层细胞cAMP含量明显高于假手术组;NCS-356 320和NCS-356 640组大鼠的脑缺血皮层细胞cAMP的含量显著低于I/R组。I/R组大鼠脑缺血皮层细胞浆内PKA四聚体水平明显低于假手术组;NCS-356 320和NCS-356 640组的PKA四聚体的水平较I/R组升高。结论:激动GHBR对大鼠局灶性脑缺血再灌注损伤具有一定的保护作用,其机制可能与Gi蛋白、cAMP、PKA信号分子有关。
Objective: To investigate the role and mechanism of γ-hydroxybutyrate receptor (GHBR) in focal cerebral ischemia-reperfusion (I / R) injury in rats. Methods: I / R model was established by using modified Longa thread occlusion method for 2 h after ischemia / 2 h reperfusion. Drugs were given to the lateral ventricle (icv) 30 minutes before ischemia and reperfusion, respectively. The 5-point scoring system was used to evaluate the neurological function. After 24 h of reperfusion, the cAMP content of cerebral cortex neurons in rats was measured by radioimmunoassay. Protein kinase A (PKA) tetramer level was determined by Western-blot. Results: The behavioral score of rats in I / R group was significantly higher than that of sham group. The score of behavior in NCS-356 640 group was significantly lower than that in I / R group. The level of cAMP in cerebral ischemia cortex in I / R group was significantly higher than that in sham operation group. The cAMP content in cerebral cortex in NCS-356 320 and NCS-356 640 groups was significantly lower than that in I / R group. PKA tetramers in cerebral cortex were significantly lower in I / R group than those in sham operation group; PKA tetramers in NCS-356 320 group and NCS-356 640 group were higher than those in I / R group. CONCLUSION: GHRP may play a protective role in focal cerebral ischemia-reperfusion injury in rats. Its mechanism may be related to Gi protein, cAMP and PKA signaling molecules.