海南医科大学学报2025，Vol.31Issue(15)：1141-1152,12.DOI:10.13210/j.cnki.jhmu.20241031.002
天麻钩藤饮通过PI3K/AKT信号通路介导细胞凋亡改善高血压合并血管性认知障碍作用机制
Mechanism of apoptosis mediated through PI3K/AKT signaling pathway by Tianma Gouteng decoction to improve spontaneous hypertension combined with vascular cognitive impairment
摘要
Abstract
Objective:To investigate the interventional effects of Tianma Gouteng Decoction on rats with spontaneous hyper-tension combined with vascular cognitive impairment model,and to observe the effects of this formula on phosphatidylinositol 3-ki-nase(PI3K)/serine/threonine kinase(AKT)signaling pathway,and to reveal its potential functional mechanism.Methods:Thirty-six male SHR rats were randomly grouped into sham operation group,model group,nimodipine group(9.375 mg/kg)and high,medium and low dose groups of Tianma Gouteng Decoction(23.750 g/kg,11.875 g/kg and 5.938 g/kg)by strict random-ized numerical table method.Six wistar rats were taken as a blank control group,and were treated with unilateral common carotid artery occlusion plus high salt diet.A rat model of spontaneous hypertension combined with vascular cognitive impairment was es-tablished by the method,followed by continuous treatment with nimodipine and different doses of Tianma Gouteng Decoction for 28d.Morris water maze test was used to test the escape latency,target quadrant residence time and the number of crossing plat-forms in each group of rats,Nissl staining was used to observe the pathological changes of neurons in rat hippocampal CA1 area and Nissl vesicles,TUNEL staining was used to evaluate the effect on neuronal apoptosis in rat hippocampal CA1 area,Western blotting was used to detect the protein expression of AKT,PI3K,p-AKT and p-PI3K in hippocampal tissues of each group of rats.Detection of protein expression and phosphorylation levels of AKT and PI3K in hippocampal tissues of rats in various groups by Western Blotting,and enzyme-linked immunosorbent assay(ELISA)was used to detect the protein expression of Caspase-3,Bcl-2 and Bax in the hippocampal tissues of rats in each group as well as the protein expression of ET-1 in serum.Results:Com-pared with the blank group and sham operation,rats in the model group had increased blood pressure,prolonged evasion latency,decreased target quadrant residence time,and decreased number of crossing platforms(P<0.01);hippocampal expression of Cas-pase-3 and Bax proteins increased significantly(P<0.01),and expression of Bcl-2 proteins decreased(P<0.01);hippocampal cell counts in the model group decreased(P<0.01),decrease in Nitrosomes,increase in TUNEL-positive cells(P<0.01),and significant decrease in phosphorylation levels of AKT and PI3K proteins(P<0.01).Compared with the model group,rats in the high,medium and nimodipine dose groups of Tianma Gouteng Decoction and the model group had lower blood pressure,reduced evasion latency,prolonged residence time in the target quadrant,and increased number of crossings of the plateau(P<0.01);pro-tein expression of Caspase-3 and Bax decreased in the high,medium and low dose groups of Tianma Gouteng Decoction and the nimodipine group(P<0.01)and Bcl-2 protein expression rose(P<0.01);hippocampal cell counts increased(P<0.01),nidus bodies increased,and TUNEL-positive cells decreased(P<0.01)in the rat.protein expression rose(P<0.01);hippocampal cell counts increased in rats(P<0.01),Nitrosomes increased,and TUNEL-positive cells decreased(P<0.01);and AKT and PI3K protein phosphorylation levels were significantly elevated(P<0.01).Conclusion:Tianma Gouteng Decoction may improve the cognitive function of SHR combined with VCI rats by promoting the phosphorylation of AKT and PI3K proteins,inhibiting the ex-pression of Caspase-3 and Bax proteins,elevating the expression of Bcl-2 proteins,and attenuating the apoptosis of hippocampal neurons.关键词
天麻钩藤饮/高血压/血管性认知障碍/神经元凋亡/磷脂酰肌醇3-激酶/丝氨酸/苏氨酸激酶Key words
Tianma Gouteng Decoction/Hypertension/Vascular cognitive impairment/Neuronal apoptosis/PI3K/AKT分类
医药卫生引用本文复制引用
张红晓,李纳川,赵凡莹,刘子旺..天麻钩藤饮通过PI3K/AKT信号通路介导细胞凋亡改善高血压合并血管性认知障碍作用机制[J].海南医科大学学报,2025,31(15):1141-1152,12.基金项目
Hospital level cultivation of the Third Affiliated Hospital of Beijing University of Traditional Chinese Medicine(BZYSY-2022-PYMS-10) 北京中医药大学第三附属医院院级培育(BZYSY-2022-PYMS-10) （BZYSY-2022-PYMS-10）
