全反式维甲酸对兔颈动脉内膜损伤和炎症反应的影响
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The Effect of All-trans Retinoic Acid on the Endometrial Injuring and Inflammatory Response in Carotid Artery of Rabbits
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    目的 通过建立兔颈动脉内膜损伤模型,观察损伤病灶内血管内膜增生状态,检测炎症相关因子即血小板活化因子(PAF)与白三烯B4(LTB4)的表达水平,探讨全反式维甲酸(ATRA)是否具有通过抗炎而稳定斑块的作用及其机制。方法 选取36只新西兰雄性健康兔,随机分为对照组、高脂组、治疗组,每组12只。每组再分为A、B、C 3个亚组,每个亚组4只。对照组给予基础饲料,高脂组与治疗组给予高脂饲料,两周后行动脉内膜空气干燥术。对照组仅暴露颈动脉但不损伤内膜(即假手术);其余两组进行空气干燥术损伤动脉内膜;治疗组于术前3天开始给予ATRA灌胃。分别于术后1、2、4周处死A、B、C 3个亚组动物,取病变血管进行形态学观察,测量所取血管横截面的内膜面积,采用酶联免疫吸附法检测兔血清PAF与LTB4的表达水平。结果 对照组未见内膜增生,PAF及LTB4有正常少量表达;高脂组内膜增生明显,管腔狭窄甚至变形,管壁不规则脂质斑点形成,PAF(281.3±14.6 ng/L)及LTB4(42.79±0.18 ng/L)表达显著增多(均P<0.05);治疗组内膜增生程度介于对照组与高脂组之间(P<0.05),PAF及LTB4的表达水平亦介于对照组与高脂组之间(P<0.05)。结论 ATRA可以显著抑制动脉内膜损伤病灶内膜增生,其机制可能与ATRA抑制PAF的激活和表达,减少炎性趋化因子LTB4的释放,从而抑制炎症反应有关。

    Abstract:

    Aim To investigate whether the all-trans retinoic acid (ATRA) will perform anti-inflammatory role and therefore to inquire into its possible mechanism of stabilizing plaques, by establishing the animal models ofcarotid artery endometrial injuring in rabbits and observing the expression level of platelet-activating factor (PAF) and leukotriene B4 (LTB4).Methods 36 New Zealand male healthy rabbits were randomly divided into three groups: contrast group (n=12), high-fat group (n=12) and treatment group (n=12), each group then were divided into three subgroups (A, B, C). Contrast group were provided basic feed while the other two groups were given fatty feed. All groups have to be suffered from artery intima air-drying technique after two weeks. Contrast group only had exposure of carotid artery but no damage to the intima others should have injury to artery intima the treatment group were administered ATRA lavage daily from 3 days before the surgery. On the 7d, 14d and 28d, the target vessels were taken out for morphological observation and measuring of intima thickening. Enzyme-linked immunosorbent assay (ELISA) method was used to detect the expression level of PAF and LTB4 in rabbit serum.Results Contrast group did not see endometrial hyperplasia, PAF and LTB4 had normal small expression. High-fat group were of endometrial hyperplasia obviously, target vessels were stenosis even deformation, PAF and LTB4 had quantity expression. The intima hyperplasia in treatment group was lower than high-fat group (P<0.05) as the same as the expression level of PAF and LTB4.Conclusion ATRA can significantly alleviate injury area endometrial proliferation, the mechanism may be related to its inhibition of PAF activation and expression, then reduce the release of inflammatory chemokines LTB4 in order to restrain the inflammatory response ultimately.

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阚冰冰,董果雄,张社华,姚如永.全反式维甲酸对兔颈动脉内膜损伤和炎症反应的影响[J].中国动脉硬化杂志,2013,21(11):993~996.

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  • 收稿日期:2013-04-15
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