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作 者:刘萍[1] 王菊英[1] 李倩[2] 王姿颖[1] 刘兆平[3] 张岫美[1]
机构地区:[1]山东大学医学院药理学研究所,山东济南250012 [2]山东省地方病防治研究所,山东济南250014 [3]山东大学新药评价中心,山东济南250012
出 处:《中国新药与临床杂志》2007年第2期109-114,共6页Chinese Journal of New Drugs and Clinical Remedies
摘 要:目的:研究黄芩苷对大鼠局灶性脑缺血-再灌注损伤后神经细胞凋亡以及半胱氨酸天冬氨酸蛋白酶(caspase)-3、热休克蛋白(HSP)70表达的影响。方法:96只Wistar大鼠随机分为假手术组、脑缺血再灌注模型组、黄芩苷组(50,100,200 mg·kg-1),以及尼莫地平(0.4 mg·kg-1)组。利用大鼠大脑中动脉内栓线阻断法制备局灶性脑缺血-再灌注损伤模型,通过HE染色、流式细胞术、免疫组化以及RT- PCR等方法,观察黄芩苷对大鼠局灶性脑缺血-再灌注损伤后脑组织病理形态学改变、神经细胞凋亡率以及caspase-3、HSP70表达的影响。结果:黄芩苷可明显改善脑缺血-再灌注损伤所致的大鼠脑组织病理形态学改变,降低神经细胞凋亡率,抑制促凋亡基因caspase-3的表达,促进抑凋亡基因HSP70的表达。结论:黄芩苷对大鼠局灶性脑缺血-再灌注损伤具有保护作用,其作用机制可能与黄芩苷抑制caspase-3表达,促进HSP70表达,从而发挥抗凋亡作用有关。AIM: To investigate the effects of baicalin on the neuronal apoptosis and the expression of caspase-3 and HSP70 after focal cerebral ischemia and reperfusion injury in rats. METHODS: Ninety-six male Wistar rats were randomized into 6 groups (n = 8) : sham operated group, ischemia-reperfusion group, nimodipine group and three baicalin (50, 100, 200 mg·kg^-1) groups. The models of focal brain ischemia-reperfusion injury was established by middle cerebral artery occlusion (MCAO). HE stain was used to observe the pathological changes. The neurone apoptotic percentage in focal cerebral ischemia and reperfusion injury were measured by flow cytometry methods (FCM). Immunohistochemistry was used to obverse the protein expression of caspase-3 and HSP70. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression of the mRNA level of caspase-3 and HSP70. RESULTS: Baicalin improved the pathological changes and inhibited apoptosis in hippocampus CA1 area significantly. Baicalin decreased the expression of caspase-3 and increased the expression of HSP70. CONCLUSION: Baicalin has the protective effects against cerebral damage induced by focal ischemia-reperfusion in rats, which may be related to inhibiting the process of the neuronal apoptosis. The mechanism of antiapoptosis effect of baicalin may be related to the inhibition of caspase-3 expression and the promotion of HSP70 expression.
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