大脑5－HT的变化及5－HT_2受体拮抗剂赛庚啶对沙土鼠脑缺血的影响

Study on changes of serotonin and the effects of cyproheptadine in gerbils following cerebral ischemia

本文研究大脑组织５－ＨＴ及其代谢产物变化以及５－ＨＴ＿２受体拮抗剂赛庚啶对脑缺血损伤的防治作用。实验共分三部分，结果是：（１）在沙土鼠急性前脑缺血模型证明，缺血１０ｍｉｎ，３０ｍｉｎ，及缺血３０ｍｉｎ再灌２ｈ，可见脑组织５－ＨＴ减少，说明脑缺血时脑组织释放５－ＨＴ增加而摄取减少，５－ＨＴ代谢产物５ＨＩＡＡ缺血后也见减少，但再灌后明显增加。（２）５－ＨＬ＿２受体拮抗剂赛庚啶可减轻沙土鼠缺血５ｍｉｎ再灌７天后海马ＣＡ＿１区神经元迟发性损伤，给赛庚啶组ＣＡ＿１区神经元数为１６８．７９±６２．５／ｍｍ，而生理盐水对照组为８４．７２±８７．３１／ｍｍ。（３）赛庚啶对沙土鼠单侧脑缺血能减少脑组织水及钠含量改善脑水肿及减少脑组织Ｃａ￣（２＋）含量。从５－ＨＴ＿２受体拮抗剂的作用说明，５－ＨＴ可通过５－ＨＴ＿２介导加重脑缺血时神经元损伤，加重脑水肿和脑组织Ｃａ＿（２＋）聚积，５－ＨＴ＿２受体拮抗剂可减轻缺血性脑损伤。

Changes of serotonin(5- HT)and 5- hydroxyindole- 3-acetic acid(5- HIAA)in cortex were measured by means of fluorimetry and the effects of 5- HT_2receptor antagonist cyproheptadine(CYP)in gerbils following cerebral ischemia wasobserved.The results showed that:(1)5- HT in cortex decresed significantly in 10min,30 min ischemia and 30 min ischemia following 2 h reperfusion; 5-HIAA decre- sed after ischemia, but increased after rep erfusion. (2 ) The delayed neuronaldeath(DND)in hippocampus CA_1 sector in gerbils subjected to 5 min ischemia fol-lowing 7 days reperfusion was abated by CYP.The neuronal number of CYP treatmentgroup was 168.79 ± 62.50/mm, while of NS group was 84.72 ± 87.31/mm.(3)Thecontents of water, sodium and calcium of unilateral cerebral ischemia decreased in CYPtreatment group. These results suggested that the release of Serotonin from nerve endingmay be increased in cerebral ischemia in gerbils and brain edema,calcium overloadmay be aggravated by 5- HT mediating with 5-HT_2. Subsequently ischemic brain damagewas abated by 5- HT_2 receptor antagonist.