补肾和脉方对老年自发性高血压大鼠下丘脑蛋白质组学的影响  

Effect of Bushen Hemai Decoction on Hypothalamic Proteomics in Rats with Elderly Spontaneous Hypertension

作　　者：史琳[1] 杨传华[1] Shi Lin;Yang Chuanhua(The Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Shandong,Jinan 250011,China)

机构地区：[1]山东中医药大学附属医院,山东济南250011

出　　处：《中国中医急症》2024年第2期209-214,239,共7页Journal of Emergency in Traditional Chinese Medicine

基　　金：山东省自然科学基金项目(ZR2019QH016);山东省中医药科技发展计划项目(2019-0100)。

摘　　要：目的探寻补肾和脉方治疗老年自发性高血压病的可能分子机制。方法选取16月龄雄性自发性高血压大鼠(SHR),采用随机数字表法随机分为2组:补肾和脉方组[10只,补肾和脉方生药浓度14.22 g/(kg·d)]和模型组(10只,生理盐水2 mL/d),以10只同龄雄性WKY大鼠作为正常对照组(生理盐水2 mL/d),共灌胃干预8周。定期观察并监测记录大鼠的收缩压和舒张压。干预结束后,取各组大鼠血清、下丘脑。ELISA法检测血清中神经肽(NPY)、去甲肾上腺素(NE)、C反应蛋白(CRP)和血管紧张素Ⅱ(AngⅡ)的含量。Label-free定量蛋白组学测序分析方法筛选下丘脑蛋白质表达谱的变化,通过生物信息学对差异蛋白进行GO富集分析,并对差异蛋白的分子功能、细胞成分和生物学途径3个方面进行功能方面的注释;对差异蛋白进行KEGG通路分析得到补肾和脉方靶蛋白及其涉及的信号通路;同时建立差异蛋白的互作网络综合分析补肾和脉方的药理机制,进而为研究老年自发性高血压寻找新的药物标志蛋白提供理论和思路。结果1)补肾和脉方能够稳步降低老年自发性高血压大鼠的收缩压、舒张压、脉压差和平均动脉压;降低大鼠血清NPY、NE、CRP、AngⅡ的水平,在一定程度上改善高血压的血管重塑。2)与模型组相比,应用补肾和脉方干预后的大鼠下丘脑中共检出2753个差异蛋白点,其中316个蛋白有统计学差异(P<0.05),201个蛋白表达升高,115个蛋白表达降低;差异蛋白主要富集于转运酶活性和离子通道活性方面。3)补肾和脉方干预老年SHR下丘脑的节点蛋白Cdc42、SIRT2、Ptk2b的表达与蛋白组学一致。结论补肾和脉方治疗老年自发性高血压的分子机制可能与其促进神经元细胞活力,维持动脉血管的稳定性等有关。Objective:To investigate the possible molecular mechanism of Bushen Hemai Decoction in the treat-ment of elderly spontaneous hypertension in rats.Methods:Male spontaneous hypertension rats(SHR)of sixteen-monthold were randomly divided into two groups:Bushen Hemai Decoction group(10 rats,with a crude drug concentration of 14.22 g/(kg·d)and model group(10 rats,2 mL/d of normal saline),and 10 male WKY rats of the same age were used as normal control group(2 mL/d of normal saline).All received gavage for 8 weeks.The systolic and diastolic blood pressure of the rats were observed and monitored regularly.After the intervention,serum and hypothalamus were collected from each group.The contents of neuropeptide Y(NPY),norepinephrine(NE),C-reactive protein(CRP)and angiotensin Ⅱ(Ang Ⅱ)in serum were detected by ELISA.Label-free quantitative proteomics sequencing analysis method were used to screen the changes in hypothalamic protein expression profile,and GO enrichment analysis of differential proteins were performed by bioinformatics,the molecular function of differential proteins were analyzed,the functional aspects of cellular components and biological pathways were annotated,the KEGG pathway analysis of the differential proteins was carried out to obtain the target proteins of Bushen Hemai Decoction and the signaling pathways involved,and the interaction network of differential proteins was established to comprehensively analyze the pharmacological mechanism of Bushen Hemai Decoction,so as to provide theories and ideas for the study of new drug marker proteins in the study of senile spontaneous hypertension.Results:1)Bushen Hemai Decoction could steadily reduce the systolic blood pressure,diastolic blood pressure,pulse pressure difference and mean arterial pressure in rats with elderly spontaneous hypertension,and reduce the serum levels of NPY,NE,CRP and Ang I,and improve the vascular remodeling of hypertension to a certain extent.2)Compared with the model group,a total of 2753 differential protein points were dete

关 键 词：老年自发性高血压病 补肾和脉方 下丘脑 蛋白质组学 大鼠 

分 类 号：R285.5[医药卫生—中药学]