定心方通过上调CD4^+CD25^+Foxp3^+调节性T细胞表达对PM2.5所致动脉粥样硬化的影响  

Effect of Dingxin Recipe in Inhibiting Atherosclerosis Induced by PM2.5 by Up-regulating CD4^+CD25^+Foxp3^+ Regulatory T Cells Expression

作　　者：万强[1] 刘中勇[1] WAN Qiang;LIU Zhong-yong(The Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine,Nanchang 330006,Chin)

机构地区：[1]江西中医药大学附属医院

出　　处：《中国实验方剂学杂志》2018年第17期139-144,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81660770);江西省自然科学基金项目(20161BAB215256);江西省卫生计生委科技计划项目(20171105);江西省卫生计生委中医药科研课题项目(2016A083)

摘　　要：目的：观察定心方（DXR）在小鼠吸入PM2．5所致动脉粥样硬化（AS）过程中对CD4＋CD25＋Foxp3＋调节性T细胞（CD4＋CD25＋Foxp3＋Tregs）表达调控的影响。方法：50只载脂蛋白E基因敲除（ApoE-1）小鼠喂食高脂饲料并吸入严重污染的自然空气，随机分为5组，DXR低、中、高剂量组分别灌胃DXR9．29，18．59，37．18g·kg-1·d-1；辛伐他汀组灌胃辛伐他汀5mg·kg-1·d-1；模型组灌胃等剂量生理盐水；10只C57BL／6J小鼠喂食普通饲料吸入过滤空气设为正常组。16周后检测小鼠血清脂质、酶联免疫吸附测定测定（ELISA）检测白细胞介素-6（IL-6），肿瘤坏死因子-α（TNF-α），白细胞介素-10（IL-10）及转化生长因子嵋（TGF巾）水平；流式细胞法检测脾脏CD4＋CD25＋Foxp3＋Tregs数量；苏木素一伊红（HE）染色观察主动脉As斑块形态学变化；蛋白免疫印迹法（Westernblot）检测主动脉AS斑块Foxp3蛋白表达。结果：与正常组比较，模型组小鼠主动脉AS斑块形成，血清脂质，IL-6及TNF-α水平明显升高，IL-10及TGF-β水平明显降低，CD4＋CD25＋Foxp3＋Tregs数量明显减少，Foxp3蛋白表达明显降低（P〈0．05）；与模型组比较，辛伐他汀组，DXR中、高剂量组小鼠AS斑块面积明显减小，血清脂质，IL-6及TNF-α水平明显降低，IL-10及TGF够水平明显升高，CD4＋CD25＋Foxp3＋Tregs数量明显增加，Foxp3蛋白表达明显增加（P〈0．05）。结论：DXR可通过上调CD4＋CD25＋Foxp3＋Tregs表达发挥抗PM2．5所致AS功效。Objective： To investigate the effect of Dingxin recipe （DXR） on the expression of CD4 ＋ CD25＋ Foxp3＋ regulatory T cells （CD4＋ CD25 ＋ Foxp3＋ Tregs） in mice during atherogenesis induced by PM2.5. Method： Fifty western-diet apolipoprotein E knockout （ApoE-/-） mice were exposed to PM2.5 and randomly divided into five groups ： model group, low-dose DXR group （ 9.29 mg-kg-1.d -1 ） , medium-dose DXR group （18.59 mg ＋ kg-1· d -1）, high-dose DXR group （37.18 mg ＋ kg-1 d -1） and simvastatin group （5 mg kg-1 d-1）. Ten normal-diet C57BL/6J mice were exposed to filtered air and included into control group. Serum levels of lipid, interleukin-6 （IL-6）, tumor necrosis factor-α （TNF-α）, IL-10 and transforming growth feactor-β （TGF-β） were detected by enzyme linked immunosorbent assay （ELISA） , CD4 ＋ CD25 ＋ Foxp3 ＋ Tregsnumber in the spleen, atherosclerotic lesion was detected by htoxylin eosin （HE） and Foxp3 protein expression was detected by Western blot in aorta were measured after 16 weeks. Result： Compared with the control group, atherosclerotic lesion, serum levels of lipid, IL-6 and TNF-α were significantly increased, while serum levels of IL- l0 and TGF-β, CD4 ＋ CD25 ＋ Foxp3 ＋ Tregs number and Foxp3 protein expression were significantly decreased in the model group （P 〈 0.05）. Compared with the model group, TNF-a were significantly decreased, while serum levels of atherosclerotic lesion, serum levels of lipid, IL-6 and IL-10 and TGF-β, CD4 ＋ CD25 ＋ Foxp3 ＋ Tregs number and Foxp3 protein expression were significantly increased in the simvastatin group, medium-dose DXR group and high-dose DXR group （P 〈 0.05 ）. Conclusion ： DXR inhibits atherosclerosis induced by PM2. 5 by up-regulating CD4 ＋CD25 ＋Foxp3 ＋ Tregs expression.

关 键 词：定心方 CD4^+CD25^+Foxp^3+调节性T细胞 PM2.5 动脉粥样硬化 

分 类 号：R22[医药卫生—中医基础理论] R24[医药卫生—中医学]