目的 歸納大鼠寒凝血瘀模型在基因表達(dá)層面的肝臟功能變化和潛在的分子標(biāo)記，并探討淫羊藿多糖（EFPS）對(duì)基因表達(dá)的影響。方法 雄性SD大鼠隨機(jī)分為3組：對(duì)照組、模型組和EFPS（38.7 mg/kg）組，將模型組和EFPS組大鼠連續(xù)15 d每天14∶00時(shí)置于冰水浴1 h，造模的同時(shí)每天給藥1次。取3組大鼠肝臟進(jìn)行轉(zhuǎn)錄組測(cè)序，通過構(gòu)建差異表達(dá)基因（DEGs）的基因本體（GO）中生物過程（BP）與京都基因和基因組百科全書（KEGG）網(wǎng)絡(luò)，同時(shí)結(jié)合基因富集分析（GSEA），分別分析并比對(duì)各組大鼠的肝臟功能變化。結(jié)果 與對(duì)照組比較，模型組大鼠肝臟基因表達(dá)變化表現(xiàn)為脂質(zhì)代謝下調(diào)、細(xì)胞生長(zhǎng)受負(fù)向調(diào)控、產(chǎn)生免疫反應(yīng)以及對(duì)于溫度的自穩(wěn)態(tài)調(diào)節(jié)；與模型組比較，EFPS組大鼠肝臟基因表達(dá)變化表現(xiàn)出免疫回調(diào)、激素調(diào)控和基因表達(dá)調(diào)控發(fā)生改變。通過二者DEGs的等量共表達(dá)模式初步確立EFPS干預(yù)寒凝血瘀模型的分子標(biāo)記為Ccl5、Cxcl13、Jund。結(jié)論 長(zhǎng)期冰冷導(dǎo)致的體寒通過大鼠肝臟表現(xiàn)出脂質(zhì)代謝下調(diào)、細(xì)胞生長(zhǎng)減緩、促進(jìn)炎癥反應(yīng)，EFPS發(fā)揮免疫和激素調(diào)節(jié)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.

R285.5

國(guó)家重點(diǎn)基礎(chǔ)研究發(fā)展計(jì)劃“973”計(jì)劃課題（2013CB531804）