全反式维甲酸对早期动脉粥样硬化大鼠模型外周调节性T细胞与辅助性T细胞17平衡的影响

发布时间：2018-09-05 12:14

【摘要】：目的建立早期动脉粥样硬化大鼠模型,并探讨其外周CD4+CD25+调节性T细胞(Treg)与辅助性T细胞17(Th17)平衡变化及全反式维甲酸对平衡的影响。方法 50只8周龄SD大鼠,随机分为对照组、高脂组、免疫组、免疫高脂组以及全反式维甲酸组,对照组、免疫组予正常饲料,其他三组予高脂饲料,免疫组、免疫高脂组以及全反式维甲酸组注射卵清白蛋白进行初始免疫和强化免疫。全反式维甲酸组同时予以全反式维甲酸灌胃,16周后获取血和动脉。检测血清脂质变化,主动脉HE染色以观察动脉病变;流式细胞术检测各组大鼠外周血Treg和Th17细胞表达率,酶联免疫吸附法检测血清相关细胞因子水平。结果成功建立早期动脉粥样硬化大鼠模型。组织形态学显示免疫高脂组内膜增生;与免疫高脂组比较,免疫组及全反式维甲酸组程度较轻,对照组及高脂组动脉完好。高脂组及免疫高脂组血清胆固醇和低密度脂蛋白较对照组、免疫组有显著增加(均P0.05),而全反式维甲酸组与其他各组比较无统计学差异。与对照组及高脂组相比,免疫组及免疫高脂组大鼠Treg细胞表达及白细胞介素10(IL-10)、转化生长因子β水平显著降低,而Th17细胞表达及IL-17、IL-6水平明显增高(均P0.05),全反式维甲酸组Treg表达及相关细胞因子水平与免疫高脂组比较显著升高,而Th17表达及相关因子水平明显降低(均P0.05)。结论免疫损伤结合高脂喂养可形成早期动脉粥样硬化大鼠模型,该模型存在Treg与Th17细胞平衡失调,全反式维甲酸可通过影响Th17/Treg平衡发挥抗动脉粥样硬化效应。
[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.
【作者单位】：安徽医科大学附属省立医院中心实验室;安徽医科大学分子生物学中心实验室;
【基金】：安徽省青年自然科学基金项目(11040606Q08) 安徽高校省级自然科学研究重点项目(KJ2011A166) 安徽医科大学校科研基金项目(2010XKJ083)资助
【分类号】：R543.5;R-332

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