地塞米松通过影响Caspase-3及NF-κB表达加重脑缺血再灌注凋亡作用

Effects of Dexamethasone on the Expressions of NF-κB and Caspase-3 in Cerebral Ischemia and Reperfusion Injury

目的:研究地塞米松是否加重脑缺血再灌注细胞凋亡及核转录因子NF-κB、Caspase-3在此过程中的作用。方法:采用线栓法建立大鼠局灶性脑缺血再灌注模型。缺血1h后生理盐水组腹腔注射0.9%氯化钠注射液(0.5mL),地塞米松组腹腔注射地塞米松[0.5mg(/kg·d)]。利用TUNEL法研究凋亡细胞的变化,应用免疫组化、原位杂交法检测NF-κB蛋白、Caspase-3mRNA的表达。结果:各缺血组凋亡细胞显著增多。地塞米松组各时点凋亡细胞数多于生理盐水组,NF-κB活化程度均明显低于生理盐水组,Caspase-3染色阳性细胞数明显高于生理盐水组(P<0.01)。结论:地塞米松加重大鼠局灶性脑缺血再灌注损伤可能是与其阻碍NF-κB蛋白活化与上调Caspase-3mRNA表达,并继而加重脑神经细胞凋亡的机制有关。

Objective： To investigate the effects of dexamethasone on the expressions of NF-κB and Caspase-3 in cell apop-tosis of focal cerebral ischemia and repeffusion injury. Methods： The rat models of focal cerebral ischemia and repeffusion were established by middle cerebral artery occlusion. Experimental group was treated with dexamethasone [0.5 mg/ （kg·d）] and the control group was treated with saline （0.5 mL） one hour after ischemia. Cell apoptosis was studied by TUNEL and the expressions of NF-κB and Caspase-3 were examined by immunohistochemistry and hybridization. Results： The number of apoptotic cell increased significantly in ischemia groups. The expression of NF-κB protein decreased significantly, Caspase-3 positive cells increased significantly and the number of TUNEL-positive apoptotic cells increased significantly in dexamethasone group compared with those in saline group （P 〈 0.01 ）. Conclusion： Down-regulating the expression of NF-κB protein and up-regulating the expression of Caspase-3 mRNA may be the causes of dexamethasone aggravating focal cerebral ischemia and repeffusion injury.