摘要
目的探讨炎性介质阻断剂AG490对大鼠局灶性脑缺血再灌注损伤后神经功能缺损、细胞凋亡及半胱氨酸蛋白酶-3(caspase-3)表达的影响。方法雄性SD大鼠被随机分为假手术组、缺血再灌注组、生理盐水组、AG490组;采用大脑中动脉线栓法制作大鼠局灶性脑缺血再灌注模型;AG490组于脑缺血即刻及再灌注后12 h分别腹腔注射AG490 1 mg/kg。再灌注24 h后对各组大鼠进行神经功能缺损评分;利用原位缺口末端标记法(TUNEL法)检测神经细胞凋亡数;应用Western Blot法检测各组脑组织磷酸化酪氨酸蛋白激酶(P-JAK2)、磷酸化信号转导和转录激活因子(P-STAT3)、caspase-3表达。结果与缺血再灌注组及生理盐水组比较,AG490组大鼠神经功能缺损评分明显减低(均P<0.05);凋亡细胞数及P-JAK2、P-STAT3、caspase-3表达明显减少(均P<0.01)。结论AG490可阻断JAK2/STAT3细胞因子信号转导通路,有效抑制caspase-3表达,减轻缺血灌注损伤后神经细胞凋亡,改善神经功能缺损症状。
Objective To explore the effects of inflammatory mediator blocker AG490 on neurological deficits, apoptosis and expression of caspase-3 following cerebral ischemia-reperfusion（I/R） in rats. Methods The male SD rats were randomly divided into the groups sham-operation, I/R, saline and AG490; and the focal cerebral I/R models were made by middle cerebral artery thread embolism method. AG490 （ 1 mg/kg ） was intraperitoneal injection in AG490 group immediate and 12 h after isehemia-repeffusion respectively. The neurological deficits score was evaluated in 24 h after I/R in each group. The number of apoptosis in cerebral tissue was examined by d-utp nick end labeling staining（TUNEL）. The expression of P-JAK2, P-STAT3, easpase-3 were detected by Western Blot. Results Compared with the groups I/R and saline, the neurological deficits score in AG490 group was significantly decreased（all P 〈0. 05）, the number of apoptosis and the expression of P-JAK2, P-STAT3, caspase-3 were also significantly decreased （all P 〈 0. 01 ）. Conclusion AG490 can effectively reduce the apoptosis, suppresses the expression of caspase-3, improve the neurological deficits after cerebral I/R via a mechanism of blocking cytokine signal transduction pathway.
出处
《临床神经病学杂志》
CAS
北大核心
2009年第3期199-202,共4页
Journal of Clinical Neurology
