淫羊藿苷对D-半乳糖诱导的脑衰老模型小鼠p53/p21信号通路的影响

Effects of Icariin on p53/p21 Signaling Pathway in D-galactose Induced Brain Aging Model Mice

目的:观察淫羊藿苷对脑衰老模型小鼠p53/p21信号通路的影响,并探讨淫羊藿苷抗衰老的可能机制。方法:将实验小鼠随机分为空白组、模型组、淫羊藿苷低剂量组和淫羊藿苷高剂量组,除空白组外,其他各组通过D-半乳糖诱导建立脑衰老模型。淫羊藿苷低剂量组和淫羊藿苷高剂量组灌胃淫羊藿苷药液,空白组和模型组灌胃等体积生理盐水。用Morris水迷宫评价各组小鼠的学习记忆能力;用ELISA检测各组小鼠血清中T-AOC、GSH-PX、GSH-ST、MDA的表达。用Real time-PCR和免疫组化检测各组小鼠海马中p53和p21的表达。结果:与空白组比较,模型组小鼠上平台潜伏期、游泳总路程和第1次抵原平台时间都明显增加(P<0.01),而小鼠穿越平台次数和目标象限时间则明显较少(P<0.01)。与模型组相比,淫羊藿苷低剂量组和淫羊藿苷高剂量组小鼠上平台潜伏期、游泳总路程和第1次抵原平台时间均有所较少(P<0.01,P<0.05),而小鼠越平台次数和目标象限时间有所增加(P<0.01,P<0.05)。与空白组比较,模型组小鼠血清中T-AOC、GSH-PX、GSH-ST明显降低(P<0.01),而MDA明显升高(P<0.01);与模型组比较,淫羊藿苷低剂量组和淫羊藿苷高剂量组小鼠血清中T-AOC、GSH-PX、GSH-ST均有不同程度升高(P<0.01,P<0.05),而MDA则有所降低(P<0.01)。与空白组比较,模型组小鼠海马中p53、p21 mRNA和蛋白表达水平升高(P<0.01)。与模型组比较,淫羊藿苷低剂量组和淫羊藿苷高剂量组小鼠海马中p53、p21 mRNA和蛋白表达水平降低(P<0.01,P<0.05)。结论:淫羊藿苷具有延缓衰老作用,其机制可能与其抑制衰老信号通路p53/p21有关。

Objective:To observe the effect of icariin on p53/p21 signaling pathway in brain aging mice and explore the possible mechanism of Icariin on anti-aging.Methods:The experimental mice were randomly divided into blank group,model group,low dose icariin group and high dose icariin group.Except blank group,other groups were induced to establish brain aging model by D-galactose.Icariin low and high dose groups were given Icariin solution by gastric lavage,while the blank group and model group were given the equal volume normal saline.Morris water maze was used to evaluate the learning and memory abilities of mice in each group,and the expressions of T-AOC,GSH-PX,GSH-ST and MDA in serum of mice in each group were detected by ELISA.The expressions of p53 and p21 in hippocampus of each group were detected by Real time-PCR and Immunohistochemistry.Results:Compared with the blank group,the incubation period,the total swimming distance and the first time to reach the original platform of the mice in the model group were significantly increased(P<0.01),while the number of crossing the platform and the target quadrant time of the mice were significantly less(P<0.01).Compared with the model group,the mice in the icariin low and high dose groups had less latency,total swimming distance and the first time to reach the original platform(P<0.01,P<0.05),while the times of crossing the platform and the time of target quadrant were increased(P<0.01,P<0.05).Compared with the blank group,the levels of T-AOC,GSH-PX and GSH-ST in serum of mice in model group were significantly decreased(P<0.01),while MDA was significantly increased(P<0.01).Compared with the model group,the levels of T-AOC,GSH-PX and GSH-ST in serum of mice in icariin low and high dose groups were all increased(P<0.01,P<0.05),while MDA was increased to some extent(P<0.01,P<0.05).Compared with the blank group,the expression levels of p53,p21 mRNA and protein increased in the hippocampus of the model group(P<0.01).Compared with the model group,the expressions of p53,p21 mRNA and protein in hippocampus of mice in icariin low and high dose groups decreased(P<0.01,P<0.05).Conclusion:Icariin has anti-aging effect,and its mechanism may be related toinhibiting p53/p21 signaling pathway.