制何首乌中大黄素对ApoE-/-小鼠动脉粥样硬化模型中JAK2/STAT3通路的影响  

Effect of Emodin from Polygonum Multiflori Radix Praeparata on JAK2/STAT3 Pathways in ApoE-/- Mice Atherosclerosis Model

作　　者：李妹娟 王和生[1] 王通渤 赖陈岑 冷传龙 LI Mei-juan;WANG He-sheng;WANG Tong-bo;LAI Chen-cen;LENG Chuan-long(Guiyang College of Traditional Chinese Medicine,Guiyang 550002,China)

机构地区：[1]贵阳中医学院

出　　处：《中国实验方剂学杂志》2018年第18期101-106,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81160473,81460670);贵州省科技厅基金项目(黔科合J字[2013]2063号)

摘　　要：目的：探讨制何首乌中大黄素抗动脉粥样硬化的作用机制并对两面神激酶2（JAK2）/信号转导及转录激活因子3（STAT3）信号通路及相关因子细胞因子信号传导抑制蛋白3（SOCS3）的影响。方法：雄性Apo E基因敲除（Apo E-/-）小鼠80只,随机均分为8组,分别为大黄素高、中、低剂量组、模型组、阳性药组、阴性组、正常组和大黄素中剂量＋AG490组（DA组）。除正常组,余7组用高脂饲料饲养,并皮下注射脂多糖,9周后停注。第10周开始小鼠给药,6周后处死。酶联免疫吸附测定法（ELISA）测定JAK2,p-JAK2,STAT3,p-STAT3及SOCS3的含量,苏木素-伊红（HE）染色检测胸主动脉病理变化,实时荧光定量聚合酶链式反应（Real-time PCR）法检测肝脏JAK2,STAT3,SOCS3 mRNA的表达。结果：与模型组比较,大黄素高、中剂量组SOCS3含量显著增加,p-JAK2,p-STAT3含量显著减少（P〈0.01）,低剂量组SOCS3含量明显增加（P〈0.05）;JAK2,STAT3无变化;各指标DA组效果不如中剂量组且两组间存在明显差异（P〈0.01）,但STAT3相对表达量中剂量组与DA组有差异（P〈0.05）;各组SOCS3 mRNA表达明显增加,JAK2,STAT3 mRNA表达明显降低（P〈0.05,P〈0.01）。HE染色切片镜下观察,大黄素高、中剂量能有效延缓动脉粥样硬化斑块形成,而低剂量的效果不明显。结论：大黄素能明显作用于Apo E-/-小鼠动脉粥样硬化病变的发生发展,该作用机制可能与其抑制JAK2/STAT3信号通路有关。Objective： To investigate the anti-atherosclerotic mechanism of emodin from Polygonum multiflori Radix Praeparata and the effect of Janus kinase 2（ JAK2）/signal transduction and activator of transcription 3（ STAT3） signaling pathway,and its related factor suppressor of cytokine signaling 3（ SOCS3）.Method： Eighty male Apo E-/-mice were randomly divided into 8 groups： emodin high,middle,and low dose groups（ 40,20,10 mg·kg-1）,model group,positive control group（ Xuezhikang,200 mg·kg-1）,negative control group（ tween-80,4 mg·kg-1）,normal control group,and middle dose of emodin ＋ AG490 group（ DA group）. In addition to the normal control group, the remaining 7 groups were fed with high-fat diet and subcutaneously injected with lipopolysaccharide,then stopped after 9 weeks. Mice were dosed on the 10 thweek and sacrificed 6 weeks later. The contents of JAK2,p-JAK2,STAT3,p-STAT3 and SOCS3 were measured by enzyme linked immunosorbent assay（ ELISA）. The thoracic aorta was stained by hematoxylin and eosin（ HE）. The expression of JAK2,STAT3 and SOCS3 mRNA was detected by Real-time PCR. Result： Compared with the model group,SOCS3 content increased（ P〈0. 01）,p-JAK2,and p-STAT3 levels decreased（ P〈0. 01） in the emodin high-and middle-dose group,and there was increased in low-dose（ P〈0. 05）. There was no change in STAT3,JAK2. The effect of DA in each index was not as good as that in moderate dose group（ P〈0. 01）,but the relative expression of STAT3 in middle dose group was significantly different from that in DA group（ P〈0. 05）. The trend of SOCS3 gene expression in each group was increased to that detected by Real-time PCR and the results of JAK2 and STAT3 gene expression were decreased. Under the HE staining microscope,high and middle doses of emodin can effectively delay the formation of atherosclerotic plaque,but the effect of low dose is not obvious. Conclusion：Emodin can significantly affect the development of atherosclerotic lesions in Apo E-/-m

关 键 词：动脉粥样硬化 大黄素 两面神激酶2/信号转导及转录激活因子3(JAK2/STAT3)信号通路 细胞因子信号传导抑制蛋白3(SOCS3) 

分 类 号：R22[医药卫生—中医基础理论] R24[医药卫生—中医学]