摘要
实验采用大鼠四血管闭塞全脑缺血模型 ,用硫堇染色法和胶质纤维酸性蛋白 (GFAP)免疫组化法 ,观察右侧脑室内注射Ⅱ型代谢型谷氨酸受体 (metabotropicglutamatereceptor 2 / 3 ,mGluR2 / 3 )阻断剂α methyl ( 4 tetrazolyl phenyl)glycine (MTPG)对海马CA1区神经元缺血耐受 (BIT)诱导的影响 ,以探讨mGluR2 / 3在BIT诱导中的作用。 5 4只大鼠椎动脉凝闭后分为 5组 :( 1)假手术组 (n =8) :游离双侧颈总动脉 ,但不夹闭 ;( 2 )单纯缺血组 (n =8) :夹闭双侧颈总动脉 8min ;( 3 )缺血预处理组 (n =8) :夹闭双侧颈总动脉 3min作为脑缺血预处理 (CIP) ,再灌注 2 4h后再行夹闭 8min ;( 4)MTPG +缺血预处理组 (n =2 2 ) :CIP前 2 0min右侧脑室注射MTPG ,其余步骤同缺血预处理组 ;MTPG的剂量分别为 0 4、0 2、0 0 4和 0 0 0 8mg ,以观察其剂量效应关系 ;( 5 )MTPG +单纯缺血组 (n =8) :右侧脑室注射MTPG0 2mg 2 4h后 ,夹闭双侧颈总动脉 8min。所有动物均在手术后或末次缺血后 7d处死 ,取材观察。结果如下 :( 1)与假手术组相比 ,单纯 8min缺血组海马CA1区组织学分级升高、锥体神经元密度降低 ,GFAP阳性表达增加 (P <0 0 5 ) ;( 2 )缺血预处理组的组织学分级、神经元密度及GFAP表达与假手术组相似 ,未见单纯缺?
To explore the role of metabotropic glutamate receptor 2/3(mGluR 2/3)in the induction of brain ischemic tolerance (BIT), the influences of mGluR2/3 antagonist α-methyl-(4-tetrazolyl-phenyl) glycine (MTPG) on the induction of BIT and expression of glial fibrillary acidic protein (GFAP) in the hippocampus were observed using thionin staining and GFAP immunohistochemical staining in a rat brain ischemic model with four-vessel occlusion (4VO). Fifty-four rats, of which bilateral vertebral arteries were occluded permanently by electrocautery, were divided into 5 groups: (1) sham operated group (n=8): the bilateral carotid common arteries (BCCA) were separated, but the blood flow was not blocked; (2) ischemia group (n=8): the blood flow of BCCA was blocked for 8 min; (3) ischemic preconditioning (IP) group (n=8): the blood flow of BCCA was occluded for 3 min as a cerebral ischemic preconditioning (CIP), and then the rats were exposed to an 8-min brain ischemic insult 24 h after the CIP; (4) MTPG+IP group (n=22): MTPG was administered 20 min before the CIP, then the rats were exposed to an 8-min brain ischemia insult 24 h after the CIP . In order to examine dosage dependency in the effect of MTPG, 4 dosages of MTPG (0.4, 0.2, 0.04 and 0.008 mg) were administered; (5) MTPG+ischemia group (n=8): an ischemic insult for 8 min was given 24 h after the administration of MTPG (0.2 mg). MTPG was injected into the right lateral cerebral ventricle. The results obtained are as follows. (1) Ischemic insult for 8 min increased the histological grade (HG) and reduced the neuronal density (ND) significantly, and also increased the expression of GFAP significantly (P<0.05 vs sham-operated group). (2) In the IP group, the above changes were not observed, indicating that CIP could protect pyramidal neurons against the ischemic insult. (3) The protective effects of CIP were blocked by MTPG, as manifested by the significant increase in HG and decrease in ND in the MTPG+IP group (P<0.05 vs sham-operated group). The changes were dose-dependent . (4) No obvious difference in the HG, ND and expression of GFAP was detected between the groups of MTPG+ischemia and ischemia. The above results indicate that MTPG blocks the induction of BIT induced by CIP, suggesting that mGluR2/3 participates in the induction of BIT.
出处
《生理学报》
CAS
CSCD
北大核心
2003年第3期303-310,共8页
Acta Physiologica Sinica
基金
ThisworkwassupportedbytheNaturalScienceFoundationofHebeiProvince (No 30 2 494)
