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目的探究芹菜素对局灶性缺血再灌注后脑组织Toll样受体4(TLR4)、核转录因子κB(NF-κB)的表达和神经细胞凋亡的影响及神经保护作用。方法采用线栓法制作大鼠局灶性脑缺血(90 min)再灌注(24 h)模型。将70只雄性SD大鼠随机分为假手术组、模型组、尼莫地平组和芹菜素(10、25 mg·kg-1)组。观察芹菜素对神经功能缺损评分及梗死体积的影响,HE染色检测脑组织形态学改变,采用免疫组化法检测缺血核心区皮质和海马CA1区TLR4、NF-κBp65的表达,透射电镜观察缺血核心区皮质和海马CA1区神经元超微结构改变,ELISA法检测血清中TNF-α、IL-6浓度,TUNEL染色检测细胞凋亡。结果与模型组比较,芹菜素组能明显改善大鼠神经缺损症状,缩小梗死体积,减轻鼠脑病理形态学改变,减少TLR4、NF-κBp65阳性细胞表达,减少血清中TNF-α、IL-6的释放及细胞凋亡数(P<0.05,P<0.01)。结论芹菜素对局灶性缺血大脑能产生神经保护作用,降低神经细胞凋亡,其机制可能与抑制脑组织内TLR4、NF-κB表达有关。
Objective To investigate the effect of apigenin on the expression of TLR4, NF-κB and neuronal apoptosis after focal ischemia-reperfusion in rats and its neuroprotective effects. Methods The rat model of focal cerebral ischemia (90 min) and reperfusion (24 h) was established by thread occlusion. Seventy male SD rats were randomly divided into sham operation group, model group, nimodipine group and apigenin group (10, 25 mg · kg -1). The effect of apigenin on neurological deficit scores and infarct volume was observed. The morphological changes of brain tissue were detected by HE staining. The expression of TLR4 and NF-κBp65 in cortex and hippocampus were detected by immunohistochemical method. The changes of ultrastructure of neurons in the cortex and hippocampus CA1 of the blood core region, the levels of TNF-α and IL-6 in the serum were detected by ELISA, and the apoptosis was detected by TUNEL staining. Results Compared with the model group, the apigenin group could significantly improve the symptoms of nerve defects, reduce the infarct volume, alleviate the pathological changes in the rat brain, decrease the expression of TLR4 and NF-κBp65 positive cells and decrease the levels of TNF-α, IL-6 Release and apoptosis (P <0.05, P <0.01). Conclusion Apigenin can protect neurons from focal cerebral ischemia and reduce neuronal apoptosis. Its mechanism may be related to the inhibition of the expression of TLR4 and NF-κB in brain tissue.