【摘要】 目的探讨高血压大鼠大脑皮层梗死同侧丘脑腹后核(ventroposterior nucleus of the thalamus,VPN)继发性轴突变性的病理过程。方法采用易卒中型肾血管性高血压大鼠(stroke-prone renovascular hypertensive rats,RHRSP)模型制备右侧大脑中动脉皮层支闭塞(middle cerebral artery occlusion,MCAO)模型,作为MCAO组。RHRSP模型仅暴露而不凝闭右侧大脑中动脉皮层支(middle cerebral artery,MCA),作为假手术组。健康配对的成年大鼠,作为正常对照组。上述3组动物分别在术后1、2、4周3个时间点,行Bielschowsky氏嗜银染色及免疫组织化学染色检测梗死同侧丘脑腹后核βA4淀粉样前体蛋白(amyloidβA4precursor protein,APP)、生长相关蛋白43(growth associated protein-43,GAP-43)和微管相关蛋白2(microtubule associated protein-2,MAP-2)的表达水平。结果与同期假手术组相比,在梗死同侧丘脑腹后核,缺血4周时检测到嗜银染色的纤维束明显减少(P<0.05);APP蛋白在缺血1周时表达开始增强并逐渐增高(P<0.05),GAP-43蛋白、MAP-2蛋白的表达水平在缺血1～2周开始下降(P<0.05)并持续降低(P<0.05)。结论轴突标志性蛋白的免疫组织化学检测方法敏感性高、能早期发现丘脑轴突的病理改变,与传统的嗜银染色方法结合,能较全面地评价VPN轴突变性的病理过程。本实验发现梗死同侧VPN的轴突变性是一个慢性进展性的过程。更多还原

【Abstract】 Objective To approach the course of secondary axonal degeneration in ipsilateral ventroposterior nucleus of the thalamus (VPN) after cerebral cortex infarction in hypertensive rats. Methods Experimental animals were divided into three groups: middle cerebral artery occlusion (MCAO) group, sham-operated group and normal control group. The model of MCAO was duplicated in the stroke-prone renovascular hypertensive rats (RHRSP) with occlusion of right distal middle cerebral artery (MCA). In the sham-operated group, the right MCA of RHRSP only exposed without occlusion. The matched healthy rats served as normal control group. At the end of 1, 2 and 4 weeks of MCAO, the animals were killed and the brains were sectioned for Bielschowsky’ s silver stainning and immunohistochemistry analysis of the expression of amyloid βA4 precursor protein (APP), growth associated protein-43 (GAP-43), microtubule associated protein-2 (MAP-2) in the ipsilateral VPN. Results The positive neural fi ber of silver stainning were decreased in MCAO group compared with in sham-operated group in ipsilateral VPN at the end of 4 weeks after ischemia (P<0.05). The expression of APP protein was beginning to increase in ipsilateral VPN at the end of 1 week after ischemia, then enhanced to a higher level from 2 through 4 weeks after ischemia (P<0.05). GAP-43, MAP-2 immunoreactivity were beginning to decrease in ipsilateral VPN at the end of 1 or 2 week after ischemia (P<0.05), then reduced to a lower level (P<0.05). Conclusion The immuno-detection of protein marker of axons was more sensitive than conventional silver staining which could fi nd the pathological change of axons at the earlier time.Combined with silver staining, it could evaluate in detail the pathological course of axonal and dendritic destroy. This study proved that a long lasting, progressive axonal degeneration developed in ipsilateral VPN after MCAO.更多还原