局灶性脑缺血大鼠脑室下区mGluR7与PCNA的表达

Expression of mGluR7 and PCNA in the Subventricular Zone in Adult Rats Following Focal Cerebral Ischemia-reperfusion

目的：动态观察代谢型谷氨酸受体7型（mGluR7）及增殖细胞核抗原（PCNA）在局灶性脑缺血大鼠不同再灌注时段前脑侧脑室的脑室下区（SVZ）中的表达,探讨神经发生的机制。方法：42只体重为280-300 g的雄性SD大鼠随机分为假手术组、再灌注不同时间段（6 h、24 h、72 h、7 d、14 d、28 d）组,每组各6只。采用改良的线栓法制备大脑右侧中动脉阻塞（MCAO）2 h的大鼠短暂局灶性脑缺血模型,用免疫组化方法检测各组SVZ的mGluR7和PCNA的表达变化。结果：与对照组相比,缺血侧SVZ的mGluR7阳性细胞于再灌注24 h开始增加（P〈0.05）,再灌注72 h达到高峰,以后逐渐回落至正常水平。再灌注72 h时非缺血侧mGluR7阳性细胞亦有明显升高（P〈0.05）。此外,mGluR7阳性细胞还可明显见于梗死区周围,尾壳核、隔外侧核、梨状内核、部分大脑皮质等区域;再灌注24 h,无论缺血侧还是非缺血侧PCNA的阳性标记细胞数目均明显增加,高峰出现在再灌注7 d（P〈0.01）,并维持较高水平至再灌注14 d,再灌注28 d时数量虽已下降,但仍明显高于对照组（P〈0.05）。再灌注72 h、7 d时,缺血侧PCNA阳性表达细胞数显著高于非缺血侧（P〈0.05）。结论：短暂脑缺血能刺激SVZ的细胞增殖和mGluR7的表达上调,后者可能参与此处由短暂局灶性脑缺血引发的神经发生过程。

Objective：To investigate the expression of metabotropic glutamate receptor 7 subtype（mGluR7）and proliferating cell nuclear antigen（PCNA）in the subventricular zone in adult rats following focal cerebral ischemia-reperfusion,and to explore its role in neurogenesis.Methods：Forty-two male Sprague-Dawley rats（weight range：280～300 g） were used in this study,and all animals were randomly devided into control group（sham operated）and middle cerebral artery obstruction（MCAO） groups with reperfusion for 6 h,24 h,72 h,7 d,14 d and 28 d respectively.The model of acute reperfusion injury after cerebral ischemia in rat was made by right middle cerebral artery occlusion.All animals were allowed 2 h ischemia and sacrificed after different durations of reperfusion.The expression of mGluR7 and PCNA was detected with an immunohistochemical approach.Results：Compared with the control group,the number of mGluR7 immunoreactive cells in the subventricular zone at 24 h after reperfusion in the ipsilateral（ischemic） side started to increase significantly（P〈0.05）and peaked at 72 h.However,at 28 d after reperfusion,the number of mGluR7 labeled cells decreased to basal level.Meanwhile,the number of mGluR7 labeled cells in the contralateral（non-ischemic） side increased significantly at 72 h after reperfusion（P〈0.05）.Additionally,the mGluR7 labeled cells were also detected in dorsal caudate putamen,lateral septal nucleus,endopiriform nucleus and some areas of cerebral cortex.A significant increase in numbers of PCNA immunoreactive cells was found in the ipsilateral subventricular zone at 72 h（P〈0.05）and with a peak at 7 day（P〈0.01）after reperfusion,then the number descended but still higher than that of basal level.The number of PCNA labeled cells in the ipsilateral side increased significantly at 72 h and 7 d after reperfusion（P〈0.05）.Conclusion：The study implies cerebral ischemia could upregulate the expression of mGluR7 and promote the proliferation of nervous stem cells in the subventricular zone following ischemia.mGluR7 could be involved in the neurogenesis following transient focal cerebral ischemia.