盐酸戊乙奎醚对大鼠脑缺血-再灌流损伤的保护作用  

Protective effect of penehyclidine hydrochloride in cerebral ischemia-reperfusion injury rats

作　　者：许铁[1] 庞涛[1] 纵雪梅[1] 梁高永[1] 王志萍[2] 耿德勤[3] 燕宪亮[1] 王厚清[1] 

机构地区：[1]徐州医学院附属医院急救中心,江苏省徐州221002 [2]徐州医学院附属医院麻醉科,江苏省徐州221002 [3]徐州医学院附属医院,神经内科,江苏省徐州221002

出　　处：《中华急诊医学杂志》2007年第9期925-928,共4页Chinese Journal of Emergency Medicine

摘　　要：目的探讨盐酸戊乙奎醚对大鼠三动脉阻断法急性全脑缺血-再灌流损伤的保护作用。方法144只雄性SD大鼠随机分为假手术组、缺血-再灌流组(生理盐水1 ml)、东莨菪碱组(0.01 mg/kg)和盐酸戊乙奎醚组(0.01 mg/kg),缺血前40 min分别腹腔注射相应药物,缺血时间为10 min,于再灌流24 h、3 d和7 d测定其行为学(开阔法、平衡木法、攀绳和肌力试验),再灌流2 h、12 h、24 h、3 d和7 d取材测定海马CA1区存活神经元数量(HE染色)、凋亡神经元数量(TUNEL染色)、bcl-2和bax蛋白表达(免疫组化染色),部分大鼠于再灌流4 d测定脑梗死体积(TTC法)。结果与缺血-再灌流组比较,盐酸戊乙奎醚组和东莨菪碱组海马CA1区凋亡神经元数量减少(P<0.01),bcl-2提前并延长表达(P<0.01),盐酸戊乙奎醚组bax表达下降(P<0.05或P<0.01)。同时,盐酸戊乙奎醚组和东莨菪碱组存活神经元数量增加(P<0.05),脑梗死体积缩小(P<0.05或P<0.01),行为学检测指标改善(P<0.05)。盐酸戊乙奎醚组较东莨菪碱组作用更加明显(P<0.05)。结论盐酸戊乙奎醚对脑缺血-再灌流损伤大鼠具有脑保护作用,并且优于同样剂量东莨菪碱。改变bcl-2/bax的比例可能是其机制之一。Objective To investigate the effect of a selective muscarinic receptor antagonist （penehyclidine hydrochloride） in three vessel occlusion model of acute global cerebral ischemia-reperfusion in rats. Method One hundred and forty-four male SD rats were randomly divided into four groups： sham operated group, vehicle treated group （saline 1 ml, i. p. ）, scopolamine treated group （0.01 mg/kg, i. p. ） and penehyclidine hydrochloride treated group （0.01 mg/kg, i. p. ） with drugs injected 40 minutes before ischemia respectively. The ischemic duration was 10 minutes. The animals were subjected to motor activity tests （open field activity test, beam-walking test and grip test） at 24 hours or on the 3rd and 7th day after reperfusion. HE staining, TUNEL staining and immunohistochemieal reactions of bax and bcl-2 were carried out at the time points of 2, 12, 24 hours, 3 and 7 days after reperfusion, TTC staining was carried out in some rats for assessment of infarction volume on the 4th day after reperfusion. Results As compared with the vehicle treated group, both penehyclidine hydrochloride treatment and scopolamine treatment decreased the numbers of apeptotic neurons （ P 〈 0.01 ）, accelerated and extended the expression of bcl-2 （P 〈 0.01 ） in the CA1 area of hippecampus, meanwhile, penehyclidine hydrochloride treatment lowered the expression of bax （ P 〈 0.05 or P 〈 0.01 ） . Both of the drug treatments increased the survival pyramidal cells （ P 〈 0.05）, attenuated the cerebral infarction volume （ P 〈 0.05 or P 〈 0.01） and prevented the motor activity impairment （P 〈 0.05）. A more significant improvement was shown in penehyclidine hydrochloride treated group than in scopolamine treated group （P 〈 0.05 ）. Conclusions Penehyclidine hydrochloride provides a protective effect on acute global cerebral ischemia-reperfusion injury rats. This effect is better than that of scopolamine in the same doses. The alteration of Bcl-2/Bax ratio may be one of the mechanisms

关 键 词：盐酸戊乙奎醚 脑缺血-再灌流损伤 细胞凋亡 BCL-2 BAX 大鼠 

分 类 号：R96[医药卫生—药理学]