普萘洛尔和美托洛尔处理对大鼠大脑局灶性缺血再灌注损伤后Bcl-2、Bax和NGF表达的影响

目的观察普萘洛尔、美托洛尔处理对大鼠大脑局灶性脑缺血再灌注损伤后Bcl-2、Bax和神经生长因子（NGF）表达规律的影响,探讨其脑保护作用的机制。方法 72只成年雄性Wistar大鼠（230g±10g）随机分为4组,假手术组、模型组、普萘洛尔给药组、美托洛尔给药组。每组又分为12h、24h、48h三个亚组。采用线栓法制备大鼠大脑中动脉局灶缺血再灌注模型,采用DNA原位末端缺口标记法（TUNEL）检测神经元凋亡;HE染色观察脑组织形态病理学变化;免疫组化法测定大鼠脑缺血再灌注不同时间Bax、Bcl-2与NGF的平均灰度值。结果与假手术组比较,模型组Bcl-2,Bax和NGF在缺血再灌注组12h升高,24h达高峰（P〈0.05）。普萘洛尔给药组和美托洛尔给药组的Bcl-2阳性细胞均较模型组明显增加（P〈0.05）,而Bax阳性细胞均较模型组则明显减少（P〈0.05）,但均多于假手术组（P〈0.05）。美托洛尔给药组的NGF阳性细胞与模型组无统计学意义,而普萘洛尔给药组的NGF阳性细胞较模型组显著减少（P〈0.05）。结论普萘洛尔、美托洛尔均可通过抑制Bax和促进Bcl-2表达来对大脑局灶缺血再灌注损伤后的神经元起保护作用。

Effect of Metoprolol and Propranolol on Bax,Bcl-2 and NGF Expression of Cerebral Ischemia-reperfusion Injury in Rats

Objective To research the neuroprotective effect of metoprolol and propranolol on expression of Bax、Bcl-2 and nerve growth factor（NGF） in the rat model with focal cerebral ischemia-reperfusion.Methods Seventy-two male adult Wistar rats were divided into sham operation group,ischemia-reperfusion group,propranolol treatment group,and metoprolol treatment group randomly.Each group was divided into 3 subgroups based on reperfusion time（12 h,24 h,48 h）.The models with focal cerebral ischemia-reperfusion injury were established by line embolism method.Pathological changes in brain tissue were studied by HE staining.Neuronal apoptosis was detected by TUNEL.Bax,Bcl-2,and NGF expression were studied by immunohistochemisery.Results The expression of Bcl-2,Bax and NGF positive cells were found after cerebral ischemia followed by reperfusion 12 h in the penumbra zone,and it reached a peak level at 24 h after reperfusion,then declined.Expression of Bax in metoprolol treatment group and propranolol treatment at all time points were distinctly lower than that in ischemia-reperfusion group,but more than that in sham group.Expression of Bcl-2 in metoprolol treatment group and propranolol treatment at all time point were distinctly more than that in ischemia-reperfusion group（P0.05）.Expression of NGF positive cells was found in metoprolol treatment group and ischemia-reperfusion group.Conclusion Metoprolol and propranolol obviously inhibit focal cerebral ischemia-reperfusion injury through down-regulation of the expression of Bax and up-regulation of the expression of Bcl-2,and show neuroprotective effect.