【摘要】：目的建立早期動脈粥樣硬化大鼠模型,并探討其外周CD4+CD25+調節(jié)性T細胞(Treg)與輔助性T細胞17(Th17)平衡變化及全反式維甲酸對平衡的影響。方法 50只8周齡SD大鼠,隨機分為對照組、高脂組、免疫組、免疫高脂組以及全反式維甲酸組,對照組、免疫組予正常飼料,其他三組予高脂飼料,免疫組、免疫高脂組以及全反式維甲酸組注射卵清白蛋白進行初始免疫和強化免疫。全反式維甲酸組同時予以全反式維甲酸灌胃,16周后獲取血和動脈。檢測血清脂質變化,主動脈HE染色以觀察動脈病變;流式細胞術檢測各組大鼠外周血Treg和Th17細胞表達率,酶聯(lián)免疫吸附法檢測血清相關細胞因子水平。結果成功建立早期動脈粥樣硬化大鼠模型。組織形態(tài)學顯示免疫高脂組內膜增生;與免疫高脂組比較,免疫組及全反式維甲酸組程度較輕,對照組及高脂組動脈完好。高脂組及免疫高脂組血清膽固醇和低密度脂蛋白較對照組、免疫組有顯著增加(均P0.05),而全反式維甲酸組與其他各組比較無統(tǒng)計學差異。與對照組及高脂組相比,免疫組及免疫高脂組大鼠Treg細胞表達及白細胞介素10(IL-10)、轉化生長因子β水平顯著降低,而Th17細胞表達及IL-17、IL-6水平明顯增高(均P0.05),全反式維甲酸組Treg表達及相關細胞因子水平與免疫高脂組比較顯著升高,而Th17表達及相關因子水平明顯降低(均P0.05)。結論免疫損傷結合高脂喂養(yǎng)可形成早期動脈粥樣硬化大鼠模型,該模型存在Treg與Th17細胞平衡失調,全反式維甲酸可通過影響Th17/Treg平衡發(fā)揮抗動脈粥樣硬化效應。
[Abstract]:Objective to establish an early atherosclerotic rat model and to investigate the changes of (Treg) and Th17 balance in peripheral CD4 CD25 regulatory T cells and the effects of all trans retinoic acid on the balance. Methods Fifty 8-week-old SD rats were randomly divided into control group, high-fat group, immune high-fat group and all-trans retinoic acid group. The control group and immune group were given normal diet, the other three groups were given high-fat diet and immunized group. Ovalbumin was injected into high fat group and all trans retinoic acid group for initial and enhanced immunization. All-trans retinoic acid group was fed with all-trans retinoic acid for 16 weeks to obtain blood and artery. The changes of serum lipid, HE staining of aorta to observe arterial lesion, the expression rate of Treg and Th17 cells in peripheral blood of rats in each group were detected by flow cytometry, and the levels of serum cytokines were detected by enzyme-linked immunosorbent assay (Elisa). Results the rat model of early atherosclerosis was established successfully. Histomorphology showed intimal hyperplasia in high fat immunized group. Compared with immune high fat group, the degree of intimal hyperplasia in immunized group and all trans retinoic acid group was lighter, and the arteries of control group and high fat group were intact. Serum cholesterol and low density lipoprotein in high fat group and immune high fat group were significantly higher than those in control group (P0.05), but there was no significant difference between all trans retinoic acid group and other groups. Compared with the control group and the hyperlipidemia group, the expression of Treg cells and the levels of interleukin 10 (IL-10) and transforming growth factor 尾 (TGF- 尾) were significantly decreased in the immunized and hyperlipidemic groups. The expression of Treg and related cytokines in all trans retinoic acid group was significantly higher than that in immune hyperlipidemia group (P0.05), while the expression of Th17 and the level of related factors were significantly decreased in all trans retinoic acid group (P0.05). Conclusion the rat model of early atherosclerosis can be established by immune injury combined with high fat feeding. There is imbalance between Treg and Th17 cells in this model. All trans retinoic acid can play an anti-atherosclerotic effect by affecting the balance of Th17/Treg.
【作者單位】： 安徽醫(yī)科大學附屬省立醫(yī)院中心實驗室;安徽醫(yī)科大學分子生物學中心實驗室;
【基金】：安徽省青年自然科學基金項目(11040606Q08) 安徽高校省級自然科學研究重點項目(KJ2011A166) 安徽醫(yī)科大學校科研基金項目(2010XKJ083)資助
【分類號】：R543.5;R-332

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