五脏温阳化瘀汤对血管性痴呆模型大鼠海马组织PI3K/Akt-mTOR信号通路的影响

Effects of Wuzang Wenyang Huayu Decoction (五脏温阳化瘀汤) on Hippocampus PI3K/Akt-mTOR Signaling Pathway in Vascular Dementia Model Rats

目的探讨五脏温阳化瘀汤治疗血管性痴呆的可能作用机制。方法 55只大鼠随机选择8只为假手术组,剩余大鼠采用双侧颈总动脉永久性结扎法制备血管性痴呆模型。将造模成功的39只大鼠随机分为中药高剂量组10只,中药低剂量组10只,吡拉西坦组10只,模型组9只。中药高、低剂量组分别给予五脏温阳化瘀汤5、1. 25 g/(kg·d)灌胃,吡拉西坦组给予吡拉西坦分散片0. 15 g/(kg·d)灌胃,假手术组和模型组每日给予等量生理盐水灌胃。2周后用Morris水迷宫测试大鼠的学习记忆能力;分别采用RT-PCR法和Western blot法检测大鼠海马组织中的磷脂酰肌醇-3-激酶(PI3K)、蛋白激酶B (Akt)和哺乳动物雷帕霉素靶蛋白(mTOR) mRNA及蛋白表达。结果与假手术组比较,模型组大鼠逃避潜伏期延长,跨越平台次数减少,海马组织PI3K、Akt、mTOR蛋白及mRNA表达升高(P <0. 05或P <0. 01);与模型组比较,中药高剂量组、吡拉西坦组大鼠逃避潜伏期、跨越平台次数增加,海马组织PI3K、AKT、mTOR蛋白及mRNA表达升高(P <0. 05或P <0. 01);中药高剂量组与吡拉西坦组各指标比较差异均无统计学意义(P>0. 05)。结论五脏温阳化瘀汤可以提高血管性痴呆模型大鼠的学习记忆能力,可能是通过调控海马组织PI3K/Akt-mTOR信号通路发挥作用。

Objective To investigate the possible mechanism of Wuzang Wenyang Huayu Decoction(五脏温阳化瘀汤)in the treatment of vascular dementia.Methods Eight rats were randomly selected from 55 rats as a sham operation group.The remaining rats were treated with bilateral common carotid artery permanent ligation to prepare the vascular dementia model.The 39 successful model rats were randomly divided into a high-dose group with 10 rats,a low-dose group with 10 rats,a piracetam group with 10 rats and a model group with 9 rats.The high-dose and lowdose groups of traditional Chinese medicine were given Wuzang Wenyang Huayu Decoction respectively 5 and 1.25 g/(kg·d)by gavage,and the piracetam group was given 0.15 g/(kg·d)of piracetam dispersible tablets by gavage.The sham operation group and the model group were given equivalent normal saline per day by gavage.After 2 weeks,Morris water maze was used to test the learning and memory ability of rats.RT-PCR and Western blot were used to detect phosphatidylinositol-3-kinase(PI3 K)and protein kinase B(Akt)in rat hippocampus,and mammalian rapamycin target protein(m TOR)mRNA and protein expression.Results Compared with the sham operation group,the escape latency of the model group was prolonged,the number of crossing platforms was decreased,and the expression of PI3 K,Akt,m TOR protein and mRNA in hippocampus was increased(P<0.05 or P<0.01).Compared with the model group,the escape latency and the number of crossing platforms increased in the Chinese medicine high dose group and the piracetam group,and the expression of PI3 K,AKT,m TOR protein and mRNA in hippocampus increased(P<0.05 or P<0.01).There were no significant differences in the indicators between the high dose group of Chinese medicine and the piracetam group(P>0.05).Conclusion Wuzang Wenyang Huayu Decoction can improve the learning and memory ability of rats with vascular dementia,which may be achieved by regulating PI3 K/Akt-mTOR signaling pathway in hippocampus.