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目的:研究仙茅苷对血管性痴呆(VD)模型大鼠海马区Caspase-3、PARP-1和雌激素受体(ER)表达的作用。方法:确立SD大鼠对照组后,用构建的血管性痴呆模型大鼠随机分成模型组、药物仙茅苷低(24 mg/kg)和高剂量(72 mg/kg)组(予以仙茅苷灌胃4周),每组8只。用药结束后,按设计用Morris水迷宫测试大鼠空间学习记忆功能;流式细胞术分析海马区神经细胞元凋亡;Caspase-3、PARP-1和ER蛋白水平用Western Blot测定;Caspase-3、PARP-1和ER mRNA表达用Realtime PCR检测。结果:Morris水迷宫试验结果显示,药物组和模型组大鼠逃避潜伏期均明显延长(P<0.05~0.01),模型组大鼠更明显(P<0.01);药物组和模型组大鼠空间探索距离百分比均降低(P<0.05~0.01),模型组大鼠降更明显(P<0.01)。与对照组比较,药物组和模型组大鼠海马神经细胞凋亡率显著提高(P<0.01),模型组大鼠更明显(P<0.01)。与对照组比较,模型组的Caspase-3、PARP-1蛋白和mRNA表达均增加(P<0.05);与模型组相比,仙茅苷各剂量组可见ER表达增加(P<0.05),Caspase-3和PARP-1表达降低(P<0.05)。与对照组比较,模型组的Caspase-3和PARP-1表达增加(P<0.01),而ER未见明显变化(P>0.05);与模型组相比,仙茅苷各剂量组ER表达均增加(P<0.01),Caspase-3和PARP-1表达不明显(P>0.05),但不同剂量仙茅苷组间未见明显差异(P>0.05)。结论:结果表明仙茅苷具有改善血管性模型大鼠空认知功能的作用是通过抑制海马区神经细胞凋亡,下调Caspase-3和PARP-1表达,上调海马ER表达实现的。
Objective: To investigate the effect of curculin on the expression of Caspase-3, PARP-1 and estrogen receptor (ER) in the hippocampus of vascular dementia (VD) model rats. Methods: After establishment of SD rats control group, the rats with vascular dementia model were randomly divided into model group, low dose of curculin (24 mg / kg) and high dose (72 mg / kg) Gavage 4 weeks), each group of 8. Morris water maze test was used to test the spatial learning and memory function of rats. The apoptosis of hippocampal neurons was analyzed by flow cytometry. The levels of Caspase-3, PARP-1 and ER were measured by Western Blot. Caspase-3 , PARP-1 and ER mRNA expression detected using Realtime PCR. Results: The results of Morris water maze test showed that the evasion latency of the drug group and the model group were significantly prolonged (P <0.05 ~ 0.01), and the model group was more obvious (P <0.01); the space exploration of the drug group and the model group (P <0.05 ~ 0.01). The rats in the model group decreased more significantly (P <0.01). Compared with the control group, the apoptosis rate of hippocampal neurons in the drug group and the model group was significantly increased (P <0.01), and the model group was more obvious (P <0.01). Compared with the control group, the expressions of Caspase-3, PARP-1 protein and mRNA in the model group were significantly increased (P <0.05). Compared with the model group, the expression of ER increased (P <0.05) -3 and PARP-1 expression decreased (P <0.05). Compared with the control group, the expressions of Caspase-3 and PARP-1 in the model group increased (P <0.01), while the ER did not change significantly (P> 0.05). Compared with the model group, (P <0.01). The expressions of Caspase-3 and PARP-1 were not significant (P> 0.05), but there was no significant difference between different doses of curculigin (P> 0.05). CONCLUSION: Curculigo can improve the expression of NF-κB in hippocampus by inhibiting the neuronal apoptosis, decreasing the expression of Caspase-3 and PARP-1 and up-regulating the expression of ER in hippocampus.