过刊浏览

多巴胺D_(1)和D_(2)受体激动剂和拮抗剂对脑缺血/再灌注损伤的影响

纵雪梅, 曾因明, 许铁, 吕建农　

徐州医学院附属医院急救中心. 徐州 221002；江苏省麻醉学重点实验室. 徐州 221002

摘要

实验应用开阔法、组织病理学方法、原位末端标记(in situterminal deoxynucleotidyl transferase-mediated de-oxy-UTP nick end labeling,TUNEL)法及免疫组织化学等方法,探讨多巴胺D1、D2受体激动剂和拮抗剂对沙土鼠前脑缺血/再灌注损伤海马CA1区神经元凋亡及凋亡相关基因bcl-2、bax表达的影响.结果显示:前脑缺血5 min可引起沙土鼠探索活动增加;再灌注3 d,海马CA1区约95%的锥体细胞凋亡;再灌注7 d,海马CA1区仅残存约2%-7%的存活锥体细胞;前脑缺血5 min可抑制bcl-2的表达并诱导bax表达增高;预先应用D2受体激动剂培高利特可减轻缺血后沙土鼠行为学异常、抑制海马CA1区锥体细胞凋亡、提高锥体细胞存活数、显著诱导bcl-2的表达并抑制bax的表达.预先应用SKF38393、SCH23390及螺哌隆对以上结果无明显影响.实验结果提示,培高利特具有确切的脑保护作用,诱导bcl-2并抑制bax的表达可能是其脑保护作用机制之一。

关键词： 脑缺血/再灌注损伤; 细胞凋亡; 多巴胺; 沙土鼠; bcl-2基因; bax基因

Effects of D_(1) and D_(2) dopamine receptor agonists and antagonists on cerebral ischemia/reperfusion injury

Zong Xuemei, Zeng Yinming, Xu Tie, Lo Jiannong

Center of Emergency, Affiliated Hospital of Xuzhou Medical College. Xuzhou 221002, China；Jiangsu Province Key Laboratory of Anesthesiology. Xuzhou 221002, China

Abstract

Gerbil forebrain ischemia/reperfusion(I/R) injury model was used to study the effects of D_1and D_2 receptor agonists and antagonists on neuronal apoptosis of hippocampal CA1 area. All animals weretested for habituation deficits in an open field test on the 1st, 3rd and 7th days after reperfusion. The animalswere then killed, and brains underwent paraffin embedding for hematoxylin-eosin staining, in situ terminaldeoxynucleotidyl transferase-mediated deoxy-UTP nick end labeling (TUNEL) staining and immunohisto-chemistry (bax, bcl-2). The result of open field test showed that the I/R group was significantly impaired(higher activity scores) when compared with the control group. Pretreatment with pergolide significantly re-duced this habituation impairment. Forebrain ischemia for 5 min resulted in extensive CA1 apoptosis on the3rd and 7th days after I/R injury.

Key words: Cerebral ischemia/reperfusion injury;Apoptosis;Dopamine;Gerbil;Bcl-2;Bax

收稿日期：　　录用日期：

通讯作者：　　E-mail:

引用本文：

纵雪梅, 曾因明, 许铁, 吕建农　. 多巴胺D_(1)和D_(2)受体激动剂和拮抗剂对脑缺血/再灌注损伤的影响[J]. 生理学报 2003; 55 (5): .

Zong Xuemei, Zeng Yinming, Xu Tie, Lo Jiannong. Effects of D_(1) and D_(2) dopamine receptor agonists and antagonists on cerebral ischemia/reperfusion injury. Acta Physiol Sin 2003; 55 (5): (in Chinese with English abstract).