摘要
目的研究γ-羟基丁酸受体(gamma-hydroxybutyrate receptor,GHBR)对大鼠局灶性脑缺血/再灌注神经细胞凋亡的影响。方法成年♂SD大鼠,分为假手术组(Sham),缺血/再灌注(Isc/R),NCS-356160、320、640μg.kg-1组(N1、N2、N3),NCS-382640+NCS-356640μg.kg-1组(NCS-382+N3),尼莫地平600μg.kg-1组(Nim)。采用改良的Longa法制备大鼠大脑中动脉栓塞(MCAO)模型。再灌24h后,一部分动物应用免疫组织化学染色法测定大鼠缺血侧大脑皮质Bax,Bcl-2,Caspase-3蛋白的表达,另一部分动物应用流式细胞仪测定神经细胞凋亡率。结果NCS-356160、320、640μg.kg-1及Nim增加缺血神经细胞的Bcl-2表达和Bcl-2/Bax比值,降低Bax、Caspase-3阳性细胞数和细胞凋亡百分率,上述作用可被NCS-382拮抗。结论激动GHBR可抑制大鼠局灶性脑缺血/再灌注损伤引起的细胞凋亡。
Aim To study the effect of gamma-hydroxybutyric acid receptor(GHBR ) on neuronal apoptosis suffering from focal cerebral ischemia-reperfusion injury in rats. Methods The male Sprague-Dawley rats weighing 240～280 g were randomly divided into seven groups: sham operation group(sham), ischemia-reperfusion group(Isc/R) ,NCS-356 160、320、640 μg·kg-1 group(N1、N2、N3),NCS-382 640+NCS-356 640 μg·kg-1 group(NCS-382+N3),and nimodipine 600 μg·kg-1 group(Nim).The middle cerebral artery occlusion(MCAO) model invented by Zea Longa with modifications was adopted. The experiment was divided into two parts after ischemia reperfusion for 24h:In the first part,we measured the cerebral expression of Bax, Bcl-2, Caspase-3 by immuneohistochemical method. In the second part,we measured neuronal apoptotic rate by flow cytometry in the ischemic cortex region. Results The expression rate of Bcl-2 and Bcl-2/Bax ratio of N1,N2,N3 and Nim groups were all higher than that of Isc/R group(P<0.01);The expression rate of Bax, Caspase-3 and neuronal apoptotic rate in N2,N3,Nim groups were lower than that of Isc/R group(P<0.05,P<0.01). The expression rate of Bcl-2 positive neurons and Bcl-2/Bax ratio of NCS-382+N3 group were lower than that of N3(P<0.05), whereas the expression rate of Bax, Caspase-3 and neuronal apoptotic rate were higher than that of N3(P<0.05,P<0.01). Conclusions The expression rate of Bcl-2 and Bcl-2/Bax ratio increased and the expression rate of Bax, Caspase-3 and neuronal apoptotic rate of ischemia neurons decreased after GHBR was activated by NCS-356, which could inhibit cell apoptosis following focal cerebral ischemia reperfusion injury in rats.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2007年第7期874-877,共4页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No39970715)
江苏省教育厅自然科学基金资助项目(No03KJB310141)
关键词
Γ-羟基丁酸受体
大鼠
脑缺血
再灌注损伤
细胞凋亡
gamma-hydroxybutyric acid receptor
rat
brain ischemia
reperfusion injury
apoptosis
