大鼠侧脑室注射腺苷A1受体反义寡聚脱氧核苷酸抑制脑缺血耐受的诱导  

INTRACEREBROVENTRICULAR ADMINISTRATION OF ADENOSINE A1 RECEPTOR ANTISENSE OLIGODEOXYNUCLEOTIDE INHIBITES THE NEUROPROTECTIVE EFFECT OF THE CEREBRAL ISCHEMIC PRECONDITIONING IN RATS

作　　者：郧晓静[1] 胡玉燕[1] 羡晓辉[1] 李淑琴[1] 孙晓彩[1] 张敏[1] 李清君[1] 李文斌[1] 

机构地区：[1]河北医科大学基础医学研究所病理生理研究室,河北石家庄050017

出　　处：《中国应用生理学杂志》2008年第4期430-433,I0010,共5页Chinese Journal of Applied Physiology

基　　金：教育部博士点基金资助(20050089001);河北省自然科学基金项目(C200500720;C2008001042)

摘　　要：目的:观察侧脑室注射腺苷A1受体(ARA1)反义寡聚脱氧核苷酸(As-ODN)对脑缺血预处理(CIP)脑保护作用的影响,进一步探讨腺苷A1受体在CIP脑保护作用中的作用。方法:将54只凝闭双侧椎动脉的Wistar大鼠分为Sham组、CIP组、损伤性脑缺血组、CIP+损伤性脑缺血组、双蒸水+CIP+损伤性脑缺血组、ARA1As-ODN组、ARA1As-ODN+CIP组、和ARA1As-ODN+CIP+损伤性脑缺血组。ARA1As-ODN的剂量分为10nmol/5μl和20nmol/5μl,溶于双蒸水中,侧脑室注射。所有动物均在Sham手术后或末次全脑缺血/再灌注后7d断头取脑,硫堇染色观察海马CA1区锥体神经元迟发性死亡(DND)情况。结果:Sham组和CIP组均未见DND。与Sham、CIP组相比,损伤性脑缺血组出现了明显的DND,表现为组织学分级(HG)升高和锥体神经元密度(ND)下降(P<0.05)。CIP可显著抑制损伤性脑缺血引起的DND。与CIP+损伤性缺血组相比,ARA1As-ODN+CIP+损伤性脑缺血组出现了显著的DND,表现为HG升高、ND降低(P<0.05),这种变化与ARA1As-ODN的剂量呈明显正相关。结论:腺苷A1受体As-ODN可阻断CIP诱导的脑缺血耐受,进一步证实了腺苷A1受体表达上调参与CIP诱导的脑缺血耐受。Aim： To further explore the role of adenosine A1 receptor in the neuroproteetive effect of cerebral ischemic preconditioning, the present study was undertaken to observe the effect of inhibiting expression of adenosine A1 receptor with adenosine A1 receptor antisense oligodeoxynucleotide （ARA1 As-ODN） on the neuroproteetive effect of cerebral ischemie preconditioning against delayed neuronal death（DND） normally induced by lethal brain ischemia. Methods： The rat 4-vessd occlusion global cerebral ischemic modal was used. Forty-eight male Wistar rats with permanent occlusion of the bilateral vertebral arteries were divided into 8 groups： Sham, CIP, brain ischemic insult, CIP ＋ brain ischemic insult, Distilled water ＋ CIP ＋ brain ischemic insult, ARA1 As-ODN, ARA1 As-ODN ＋ CIP,ARA1 As-ODN ＋ CIP ＋ brain ischemic insult（two doses of 10 nmol/5μl and 20 nmol/5 μl were used） groups. ARA1 As- ODN was dissolved in distilled water and injected into the right lateral cerebral ventricle. To illustrate the profile of DND, histological grade（HG） and neuronal density（ND） in the CA1 region of the hippocampus were examined 7 d after the sham operation or the last time of ischemia under thionin staining. Results： The HG and ND in CIP group were similar to those in sham group. Brain ischemic insult induced obvious DND as represented with the increase in HG and decrease in ND significantly（P 〈 0.05 vs sham and CIP groups）. In CIP ＋ ischemic insult group, no obvious DND was observed, which indicated that CIP protected pyramidal neurons against the ischemic insult. While the administration of ARA1 As-ODN in ARA1 As-ODN ＋ CIP ＋ brain ischemic insult group caused obvious increase in HG and decrease in ND compared with CIP ＋ brain ischemic insult group（P 〈 0.05） in a dose dependent manner, which indicated that the neuroprotective effect of CIP against DND of hippocampal pyramidal neurons normally induced by ischemie insult was inhibited by the administration of ARA1 As-ODN. Conc

关 键 词：脑缺血预处理 腺苷A1受体 腺苷A1受体As-ODN 海马 大鼠 

分 类 号：R363[医药卫生—病理学]