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益肺宣肺降浊方抗血管性痴呆的作用机制研究

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目的 探讨益肺宣肺降浊方(YFXF)抗血管性痴呆(VD)的作用机制。方法 通过网络药理学方法获取YFXF差异表达作用靶点(YDEGs);利用列线图模型从YDEGs中筛选高风险基因;基于高风险基因从广义线性、支持向量机、极限梯度上升和随机森林模型中筛选最优机器学习模型。采用双侧颈总动脉闭塞术构建大鼠VD模型，并随机分为模型组、YFXF组(12。18 g/kg，以生药总量计)，另设假手术组，每组6只。评价YFXF对VD大鼠行为学(以逃避潜伏期和穿越平台次数为指标)、大脑皮层组织病理形态学变化以及分泌磷酸蛋白1(SPP1)/磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(又名Akt)信号通路相关蛋白及SPP1 mRNA表达的影响。结果 共获得6个YDEGs，其中SPP1、CCL2、HMOX1、HSPB1可能是VD的高风险基因;基于高风险基因的广义线性模型预测准确性最高(曲线下面积为0。954)。与模型组比较，YFXF可显著缩短VD大鼠的逃避潜伏期，显著增加穿越平台次数(P＜0。05);可改善大脑皮层组织神经元固缩和坏死等病理损伤，显著降低SPP1蛋白及mRNA的表达水平(P＜0。05)，显著升高PI3K、Akt蛋白的磷酸化水平(P＜0。05)。结论 VD高风险基因SPP1、CCL2、HMOX1和HSPB1可能是YFXF的重要作用靶点;YFXF可能通过下调SPP1蛋白及mRNA的表达、激活PI3K/Akt信号通路来发挥抗VD作用。
Study on the mechanism of Yifei xuanfei jiangzhuo formula against vascular dementia
OBJECTIVE To investigate the mechanism of Yifei xuanfei jiangzhuo formula(YFXF)against vascular dementia(VD).METHODS The differentially expressed genes of YFXF(YDEGs)were obtained by network pharmacology.High-risk genes were screened from YDEGs by using the nomogram model.The optimal machine leaming models in generalized linear,support vector machine,extreme gradient boosting and random forest models were screened based on high-risk genes.VD model rats were established by bilateral common carotid artery occlusion,and were randomly divided into model group and YFXF group(12.18 g/kg,by the total amount of crude drugs),and sham operation group was established additionally,with 6 rats in each group.The effects of YFXF on behavior(using escape latency and times of crossing platform as indexes),histopathologic changes of cerebral cortex,and the expression of proteins related to the secreted phosphoprotein l(SPPl)/phosphoinositide 3-kinase(PI3K)/protein kinase B(aka Akt)signaling pathway and the mRNA expression of SPPl in cerebral cortex of VD rats were evaluated.RESULTS A total of 6 YDEGs were obtained,among which SPP1,CCL2,HMOX1 and HSPB1 may be high-risk genes of VD.The generalized linear model based on high-risk genes had the highest prediction accuracy(area under the curve of 0.954).Compared with the model group,YFXF could significantly shorten the escape latency of VD rats,significantly increase the times of crossing platform(P＜0.05);improve the pathological damage of cerebral cortex,such as neuronal shrinkage and neuronal necrosis;significantly reduce the expressions of SPP1 protein and mRNA(P＜0.05),while significantly increase the phosphorylation levels of PI3K and Akt(P＜0.05).CONCLUSIONS VD high-risk genes SPP1,CCL2,HMOX1 and HSPB1 may be the important targets of YFXF.YFXF may play an anti-VD role by down-regulating the protein and mRNA expressions of SPP1 and activating PI3K/Akt signaling pathway.

Yifei xuanfei jiangzhuo formulavascular dementianetwork pharmacologynomogram modelmachine learning modelSPP1/PI3K/Akt signaling pathway

卓桂锋、陈炜、张金枝、黄德庆、袁炳茂、蒲珊珊、朱小敏、廖乃彬、苏明阳、陈湘怡、符钰岚、吴林

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广西中医药大学第一附属医院脑病科,南宁 530022

广西中医药大学第一临床医学院,南宁 530022

广西中医药大学壮医药学院,南宁 530200

广西中医药大学科学实验中心,南宁 530200

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益肺宣肺降浊方 血管性痴呆 网络药理学 列线图模型 机器学习模型 SPP1/PI3K/Akt信号通路

国家自然科学基金项目国家自然科学基金项目国家中医药管理局高水平中医药重点学科(中医内科学)建设项目广西中医药大学研究生教育创新计划项目广西中医药大学研究生教育创新计划项目广西中医药大学研究生教育创新计划项目

8237438782160885zyyzdxk-2023166YCBXJ2023009YCBXJ2023029YCSW2023384

2024

10.6039/j.issn.1001-0408.2024.18.04

中国药房
中国医院协会,中国药房杂志社

中国药房

CSTPCD北大核心
影响因子：0.956
ISSN：1001-0408
年,卷(期)：2024.35(18)