胚中脑黑质移植入震颤麻痹模型大鼠脑内的实验研究

Brain Transplantation with The Substrantia Nigra of Fetal Mesencephalon in Rat As Paralysis Agitans Model

将6 - 羟基多巴胺(6 - OHDA) 分两点注入SD大鼠左侧中脑黑质内侧端,制成震颤麻痹模型,毁损后6 ～8 周,用胚龄14～16 天同种胚鼠中脑黑质细胞悬液植入模型鼠尾壳核。实验分正常对照组,模型对照组,单纯胚中脑黑质移植组(MS组) ,含层粘蛋白Laminin 胚中脑黑质移植组(LMS组) ,含雪旺氏细胞胚中脑黑质移植组(SMS组) 。于移植后2 ～4 个月分别测试旋转试验,MS组、LMS组及SMS组与模型组间均有显著差异(P< 0-01) 。动物经测试后处死。脑切片观察发现,损伤侧中脑黑质DA神经元95% 以上死亡,移植组织位于尾壳核背侧或突入侧脑室,LMS组移植区> SMS组移植区> MS组移植区。三个移植区均见TH、GABA 免疫阳性细胞,其形态及大小与正常对照侧中脑黑质所见相似。LMS组与SMS组多巴胺阳性细胞突起较MS组多且长。本实验证明中脑黑质移植物Laminin 与雪旺氏细胞均能促进DA能神经元突起生长。

Paralysis Agitans (PA) rat model was produced by injection of 6-hydroxydopamine (6-OHDA) into the right medial part of substantia nigra. 6-8 weeks post lesion, fetal (E 14-15) substantia nigra cell suspension was implanted into the caudate putamen (CP) of rats, then dvided into five groups: group I normal control (n=4), group Ⅱ model control (n=4), group Ⅲ transplanted with fetal substantia nigra cell suspension (n=6, MS group), group Ⅳ implanted with substantia nigra cell suspension containing laminin (n=6, LMS group), group Ⅴ grafted with substanti nigra cell suspension containing the cultured schwann cells (n=6, SMS group). 2-4 months after grafting, the rotation tests were carried out. The results showed that there were significant differences between grafted group and model control group at 3-4 months. After the hehavioural test, the rat brain was investigated morphologically. About 95% DA neurons of the lesioned substantia nigra of fetal mesencephalon were died and the graft was located at the dorsal part of caudate putamen and projected into the lateral ventricle. The volume of the graft area of LMS group was larger than that of SMS group and the volume of the graft area of SMS group was larger than that of MS group. TH, GABA positive neurons were found in the graft area of the three grafted groups and their shape and size were similar to those of normal substantia nigra of fetal mesencephalon. The processes of DA positive neurons in the graft of LMS group and SMS group were more and longer than that in the graft of MS group. The results indicated that laminin and cultured schwann cells in the graft area of the substantia nigra of fetal mesencephalon may supports the neuronal survival and growth in vivo.