脑缺血再灌注损伤后神经细胞凋亡及Bcl-2、Bax蛋白表达与罗非昔布的影响

目的观察大鼠局灶性脑缺血再灌注损伤后脑梗死面积的变化、脑组织神经细胞凋亡、Bcl2与Bax蛋白表达以及罗非昔布的保护作用。方法线栓法制备大鼠大脑中动脉闭塞2h/再灌注24h模型,于再灌注开始时灌胃给予罗非昔布。TTC染色观察脑梗死面积,TUNEL法检测神经细胞凋亡,免疫组化法检测脑组织Bcl2和Bax蛋白表达。结果损伤侧脑组织出现明显梗死灶,神经细胞凋亡率与Bax蛋白表达均明显升高,Bcl2/Bax比值明显下降。罗非昔布1.12、2.24mg·kg-1均可明显减少脑梗死面积,2.24mg·kg-1剂量还可显著降低神经细胞凋亡率与Bax蛋白表达,增高Bcl2蛋白表达与Bcl2/Bax比值。结论选择性COX2抑制剂罗非昔布可促进Bcl2蛋白表达并减少Bax蛋白表达,上调Bcl2/Bax比值而抑制神经细胞凋亡,从而明显改善缺血再灌注引起的脑损伤。

Apoptosis of the neurocytes and the expression of Bcl-2 and Bax proteins after focal cerebral ischemia-reperfusion injury in rats and the effects of Rofecoxib

Aim To observe the infarct size, apoptosis of the neurocytes,the expressions of Bcl-2 and Bax pro-teins after focal cerebral ischemia-reperfusion injury (CIRI) in the brain tissue of rats and the protective effects of rofecoxib.Methods The model of local CIRI was induced by reversible middle cerebral artery occlusion (MCAO) with inserting a thread through internal carotid artery,2 h occlusion followed by 24 h reperfusion.Rofecoxib was administrated (ig) at the reperfusion initiation. Using TTC staining technique to measure the infarct size of brain,TUNEL technique to examine apoptosis of the neurocytes,immunohistochemical method to examine the expression level of Bcl-2 and Bax proteins in brain tissue.Results After focal CIRI,the infarct focus of brain was showed,both apoptosis rate of the neurocytes and Bax protein expression were significantly increased and the ratio of Bcl-2 to Bax was significantly reduced.With the use of both 1.12 and 2.24 mg·kg -1 doses of rofecoxib,the brain infarct size was dramatically reduced. With the use of 2.24 mg·kg -1 dose of rofecoxib,both apoptosis rate of the neurocytes and Bax protein expression were significantly decreased,both Bcl-2 protein expression and the ratio of Bcl-2 to Bax were significantly higher than that in the group Model.Conclusion The highly selective COX-2 inhibitor rofecoxib may increase Bcl-2 protein expression and decrease Bax protein expression then increase the ratio of Bcl-2 to Bax and so reduce the neurocytes apoptosis in brain tissue thus significantly improve the brain injury after CIRI.