小檗碱对大鼠全脑缺血后海马的保护作用

PROTECTIVE EFFECT OF BERBERINE ON RAT HIPPOCAMPUS AGAINST CEREBRAL ISCHEMIA

本研究室以往曾发现小檗碱具有预防脑缺血短期（７ｄ）再灌流海马ＣＡ１迟发性神经元坏死（ＤＮＤ）的作用。本研究采用Ｐｕｌｓｉｎｅｌｌｉ－Ｂｒｉｅｒｌｅｙ四血管阻塞（４ＶＯ）致大鼠全脑缺血模型，观察了小檗碱对脑缺血（２ｍｉｎ）长期再灌流后海马的影响，并对脑缺血经短、长期再灌流对照及用药组大鼠进行了Ｍｏｒｒｉｓ水迷宫学习记忆能力检测。结果显示，小檗碱能有效的保护海马ＣＡ１区锥体细胞免于脑缺血后ＤＮＤ，经长期（３个月）再灌流后这种保护作用依然存在，细胞密度为１６８个／ｍｍ，占正常８０．５％；对脑缺血经长期再灌流引起的海马ＣＡ２、ＣＡ３、ＣＡ４继发性神经无死亡也有明显的对抗作用。脑缺血短期（１０ｄ）再灌流后，大鼠表现为明显的学习障碍，潜伏期延长，但经多次训练后，大鼠在原平台象限泳距比其它非平台象限都显著长，表明尚有良好的空间记忆能力；脑缺血经长期再灌流后，其空间学习障碍加重、记忆能力也受到严重影响。而用药组缺血大鼠无论短期或长期再灌流后，均保存了良好的空间学习、记忆能力。表明脑缺血经长期再灌流后，海马的形态和学习、记忆能力比短期再灌时将进一步受损害，而小檗碱不但对短期再灌流有保护作用，对长期再灌流的进一步损害也有明显的?

Previously our department's studies demonstrated that berberine effectively protects neurons in hippocampal CA_1 fromdel ayed neuronal death (DND) after 20 min. cerebral ischemia followed by 7 days reperfusion in rat. Four vessele occlusion(4VO) model as described previously by pulsinelli-Brierley was used in this experiment. Morris water maze tests includingplace navigation test and spatial probe test were used for control and ischemic animals behavioural study after short or longterm reperfusion. The results demonstrated that: After cerebral iscvhemia and long-term reperfusion, CA_1 pyramidal neurons were lost almost completely,also,the cell loss in CA2, CA3 of hippocampus was severe. In berberine administratiomgroup,after long-term reperfusion, the alignment of CA1 pyramidal Cells of post-ischemia hippocampus was normal, with cell density 168/mm, the cell density of CA2, CA3, CA4 was normal. The difference between berberine administration and ischemia control groups was significant. After short or long term reperfusion the ischemic animals needed more escape time(latency)than the sham-opersted animals(p< 0.01) respectvely in place navigation test. But in spatial probe test, only long-term reperfusion group rats did not swim longer distance (29. 9% ) in platform quadrant than in the others in spatial probetest. In berberine administration groups, after either short or long-term reperfusion, the latencies were not different fromsham-operated animals respectively in place navigation test. In spatial probe test, both two berberine groups animals swama longer distance in platform quadrant(38. 2%, 35. 6%) than in other three quadrants. Berberine effectively protects CA4neurons in hippocampus from DND or progressed death after ischemia and long-term reperfusion, Furthermore, the berberine protected post-ischemia hippocampus has normal spatial learning and memory function.(Figure 5 on plate 52)