γ-羟基丁酸受体-Gi蛋白信号通路在大鼠局灶性脑缺血再灌注损伤中的作用  

Effect of gamma-hydroxybutyric acid receptor and Gi protein signal way on focal cerebral ischemia-reperfusion injury in rats

作　　者：杨其侠[1,2] 秦浩[2] 王允[1] 秦伟[1] 谷淑玲[1] 

机构地区：[1]徐州医学院药理学教研室,江苏徐州221002 [2]山东枣庄市立医院,山东枣庄277102

出　　处：《中国医院药学杂志》2011年第22期1851-1854,共4页Chinese Journal of Hospital Pharmacy

基　　金：江苏省教育厅自然科学基金资助项目(编号:03KJB310141)

摘　　要：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 effect and mechanism of gamma- hydroxybutyric acid receptor （GHBR）on cerebral ischemia-reperfusion injury in rats. METItODS The ripe male Sprague-Dawley rats were randomly divided into five groups. These groups were administered NCS-356 in right lateral cerebral ventricle. The middle cerebral artery occlusion （MCAO） model referring to Longa＇s method with modifications was adopted. The effect of GHBR on behavioral consequence of MCAO rats was studied 2h after ischemia reperfusion. After 24 h of isehemia reperfusion, part animals＇ ischemic cortexes were used to measure the content of cyclic adenosine monophosphate（cAMP） by radioimmunoassay; another part animals ischemic cortexes were used to measure the protein kinase A （PKA） activity by Western blotting. RESULTS The ethology score in rats of I/R group had statistically significance compared with the sham group. The neurological function score in NCS-356 640 group was obviously lower than that in I/R group. The content of cAMP in I/R group was higher than the sham group. The content of cAMP in NCS-356 320 and NCS-356 640 groups were lower than the I/R group. The level of tetrameric PKA of I/R group was lower than the sham group obviously. The level of tetrameric PKA in NCS-356 320 and NCS-356 640 groups were higher compared with I/R group. CONCLUSION Activating GHBR has protective effects on ischemic brain injury. The neuroprotective effect is related with the decreased content of cAMP and the suppressed activity of PKA in MCAO rats.

关 键 词：Γ-羟基丁酸受体 大鼠 脑缺血再灌注 环磷酸腺苷 蛋白激酶A 

分 类 号：R965.1[医药卫生—药理学] R971.2[医药卫生—药学]