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作 者:赵金椽 王宇[2] 刘树民[2] ZHAO Jinchuan;WANG Yu;LIU Shumin(Heilongjiang University of Chinese Medicine,Harbin 150040,China;Institute of TCM,Heilongjiang University of Chinese Medicine,Harbin 150040,China)
机构地区:[1]黑龙江中医药大学,黑龙江哈尔滨150040 [2]黑龙江中医药大学中医药研究院,黑龙江哈尔滨150040
出 处:《药物评价研究》2021年第9期1862-1868,共7页Drug Evaluation Research
基 金:国家重点基础研究发展计划“973”计划课题(2013CB531804)。
摘 要:目的归纳大鼠寒凝血瘀模型在基因表达层面的肝脏功能变化和潜在的分子标记,并探讨淫羊藿多糖(EFPS)对基因表达的影响。方法雄性SD大鼠随机分为3组:对照组、模型组和EFPS(38.7 mg/kg)组,将模型组和EFPS组大鼠连续15 d每天14∶00时置于冰水浴1 h,造模的同时每天给药1次。取3组大鼠肝脏进行转录组测序,通过构建差异表达基因(DEGs)的基因本体(GO)中生物过程(BP)与京都基因和基因组百科全书(KEGG)网络,同时结合基因富集分析(GSEA),分别分析并比对各组大鼠的肝脏功能变化。结果与对照组比较,模型组大鼠肝脏基因表达变化表现为脂质代谢下调、细胞生长受负向调控、产生免疫反应以及对于温度的自稳态调节;与模型组比较,EFPS组大鼠肝脏基因表达变化表现出免疫回调、激素调控和基因表达调控发生改变。通过二者DEGs的等量共表达模式初步确立EFPS干预寒凝血瘀模型的分子标记为Ccl5、Cxcl13、Jund。结论长期冰冷导致的体寒通过大鼠肝脏表现出脂质代谢下调、细胞生长减缓、促进炎症反应,EFPS发挥免疫和激素调节作用。Objective To investigate the function variation and potential biomarkers of the cold accumulation-caused blood stasis model(CABS model) via differential gene expression of the liver, and explore the pharmacological mechanism of Epimedii Folium polysaccharide(EFPS) on the CABS model. Methods Totally 30 male SD rats were randomly divided into three groups: control group, model group and EFPS group. The rat in model group was induced by 15 d ice-water bath, 1 h/d;The rat in EFPS group were ig administered with dose of 38.7 mg/kg and volume of 10 mL/kg, meanwhile the rat in control group and model group were given the same amount of distilled water. After the liver RNA-seq of each group, GOBP and KEGG networks based on the differential expressed genes(DEGs) were constructed to analyze the liver function variation among the three groups, combined with GSEA parallelly. Results Compared with the control group, liver of rats in model group mainly presented down regulation of lipid metabolism, negative regulation of cell growth, immunoreaction and temperature homeostasis;compared with model group, liver of rats in EFPS group presented immune call-back and regulation of hormone levels and gene transcription. Three biomarkers for EFPS intervening the CABS model were preliminarily established by recognition of equivalent DEGs co-expression(synchronized callback of Ccl5, Cxcl13 and Jund).Conclusion Rat CABS model presented depression of lipid metabolism and cellular growth along with immunoreaction at liver;EFPS performed potential regulating efficacy on the CABS model at the level of immune and hormone.
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