大鼠局灶性脑缺血时活化小胶质细胞和巨噬细胞上调TGF-β_1、NGF、和GDNF的表达及意义

Increased TGF-β_1,NGF,and GDNF expression in active microglia and macroglia in focal cerebral ischemia in rats

目的 研究早期活化小胶质细胞和巨噬细胞在局灶性脑缺血性损伤中的作用。方法 阻塞大鼠大脑中动脉 2 h再灌流 0 .5～ 4 8h制成局灶性脑缺血模型 ,免疫组化法观察转化生长因子 ( TGF-β1 )、神经生长因子( NGF)和胶质源性神经营养因子 ( GDNF)在胶质细胞的表达特点。结果 正常组和假手术组小胶质细胞 TGF-β1阴性 ,再灌流 3 h组髓质小胶质细胞呈弱阳性 ,再灌流 6～ 4 8h缺血区皮质、尾壳核和视前区活化小胶质细胞呈强阳性 ;正常组和假手术组内囊、胼胝体等处的髓质小胶质细胞 GDNF、NGF呈弱阳性 ;再灌流 4 8h位于视前区的梗死周边区活化小胶质细胞和巨噬细胞 GDNF呈中等阳性 ;再灌流 0 .5 h组视前区的脑膜巨噬细胞 NGF呈强阳性 ,再灌流 12 h组视前区、尾壳核有少量的活化小胶质细胞呈弱阳性 ;再灌流 2 4～ 4 8h组位于视前区的梗死周边区内层有一圈强阳性的巨噬细胞。结论 活化小胶质细胞、巨噬细胞强力上调 TGF-β1 、NGF、GDNF表达且呈明显的次序性 ,提示缺血再灌流早期小胶质细胞活化对神经元具有一定的神经保护作用。

Objective To research the involvement of the early active microglia and macroglia during the focal cerebral ischemia in rats. Methods The focal cerebral ischemia was established by occluding middle cerebral artery for 2hours and reperfusing 0.5~48hours. The immunohistochemical method was used to study TGF-β 1,NGF,and GDNF expression in active microglia and macroglia. Results In normal group and sham operated group,the microglia showed TGF-β 1 negative. At 3hours of reperfusion,Microglia in medullas showed weakly TGF-β 1 positive. At 6~48hours of reperfusion,Microglia in ischemic cortex,caudate putamen and preoptic area showed strongly TGF-β 1 positive. In normal group and sham-operated group,Microglia in medullas including internal capsule and corpus callosum appeared weakly NGF as well as GDNF weakly positive. At 48hours of reperfusion,the active microglia and macroglia of periinfarct area located in preoptic area showed GDNF moderately positive. In contrast,macroglia in meninges of preoptic area appeared NGF strongly positive at 0.5hour of reperfusion. A few of active microglia and macroglia in preoptic area,caudate putamen weakly expressed NGF at 12hours of reperfusion. Furthermore,the active microglia and macroglia in periinfarct strongly expressed NGF at 24~48hour of reperfusion. Conclusion Active microglia and macroglia strongly and orderly up-regulated the expression of TGF-,NGF,and GDNF. These data suggest that the active microglia and macroglia at early time of ischemia-reperfusion possible protect neurons from ischemic injury.