盐酸戊乙奎醚预处理对大鼠脑缺血/再灌注损伤所致脑梗死体积和神经元凋亡的影响

乙酰胆碱(Ach)是脑内经典的兴奋性递质,作用于M型和N型胆碱受体,与大脑的多种高级神经功能有关。研究发现,脑缺血时Ach释放异常增加,若干胆碱酯酶抑制剂对神经元有损害作用[1]。也有研究表明Ach可加强谷氨酸(G lu)诱导的培养海马神经元变性,且这种作用是通过M型胆碱受体来实现的。G lu和Ach可能在缺血性脑损伤中有放大的协同作用[2]。脑内突触前N型胆碱受体激活后也能够增加包括G lu在内的多种递质的释放[3]。本实验选用对M型和N型胆碱受体都有阻滞作用的新型胆碱能受体阻滞剂盐酸戊乙奎醚为研究药,以东莨菪碱为阳性对照药,通过观察脑…

Effect of pretreatment with penehyclidine hydrochloride on cerebral infarction volume and neuronal apoptosis in murine models of cerebral ischemia-reperfusion injury

Objective To investigate the effect of a selective muscarinic receptor antagonist(penehyclidine hydrochloride) on three vessel occlusion model of acute global brain ischemia-reperfusion in rats.Methods One hundred and forty-four SD rats were randomly divided into four groups:sham operated group,vehicle pretreated group(saline 1 ml,i.p.),scopolamine pretreated group(0.01 mg/kg,i.p.) and penehyclidine hydrochloride pretreated group(0.01 mg/kg,i.p.) with drugs injected 40 min before ischemia respectively.The ischemic duration was 10 min.H-E staining,TUNEL staining and immunohistochemical reactions of bax and bcl-2 were carried out at the time points of 2 h,12 h,24 h,3 d and 7 d after reperfusion.Some animals were subjected to TTC staining for assessment of infarction volume 4 d after reperfusion.Results As compared with the vehicle pretreated group,both penehyclidine hydrochloride pretreatment and scopolamine pretreatment accelerated and extended the expression of bcl-2(P<0.01) in the CA1 subfield of hippocampus,meanwhile,penehyclidine hydrochloride pretreatment lowered the expression of bax(P<0.05 or P<0.01).Both of the drug pretreatments increased the survival pyramidal cells,decreased the numbers of apoptotic neurons and attenuated the cerebral infarction volume(P<0.05 or P<0.01).There was a more significant improvement in penehyclidine hydrochloride pretreated group than in scopolamine pretreated group in the same doses(P<0.05).Conclusion Penehyclidine hydrochloride may provide neuroprotection in acute global ischemia-reperfusion injury rats by altering the bcl-2/bax ratio.