首页|柚皮素通过调控平滑肌细胞TIMP-3表达促进动脉粥样硬化斑块稳定

柚皮素通过调控平滑肌细胞TIMP-3表达促进动脉粥样硬化斑块稳定

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  • 国家科技期刊平台
  • NETL
  • NSTL
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[目的]探究柚皮素对动脉粥样硬化斑块胞外基质重构和斑块稳定性的影响.[方法]分离原代小鼠血管平滑肌细胞,进行不同剂量的柚皮素处理.对高脂诱导的ApoE-/-小鼠进行柚皮素灌胃16周,天狼星红-苏木精染色分析主动脉根部斑块坏死核面积、斑块内胶原含量和纤维帽厚度,Van Gieson染色检测弹力蛋白降解,明胶酶谱法和荧光标记明胶法检测斑块内基质金属蛋白酶(MMP)活性.[结果]柚皮素(50 μmol/L)促进平滑肌细胞信号转导及转录活化因子6(STAT6)磷酸化和组织型基质金属蛋白酶抑制剂3(TIMP-3)的转录活性,TIMP-3的表达升高3.1倍(P＜0.001).柚皮素(80 mg/kg)处理后,与对照组相比,主动脉根部斑块坏死核面积降低53％(P＜0.01)、纤维帽厚度提高近50％(P＜0.05),弹力纤维降解程度降低.同时,柚皮素促进斑块内TIMP-3的表达,斑块内MMP活性也相应降低.慢病毒介导的体内抑制TIMP-3表达可降低柚皮素对斑块稳定的保护作用.[结论]柚皮素通过提高平滑肌细胞内TIMP-3表达,改善细胞外基质成分,促进动脉粥样硬化斑块稳定.
Naringenin promotes atherosclerotic palque stability by regulating the expression of TIMP-3 in smooth muscle cells
Aim To investigate the effects of naringenin on atherosclerotic plaque extracellular matrix remodeling and plaque stability.Methods Murine vascular smooth muscle cells were isolated and treated with various doges of naringenin.ApoE-/-mice were fed with high-fat diet and received naringenin by lavage for 16 weeks.Intraplaque nec-rotic core,contents of collagen and fibrous cap thickness were measured by Sirius red-Haematoxylin staining.Elastin was detected by Van Gieson staining.Matrix metalloproteinase(MMP)activity was determined by gelatin zymography and fluorescence-gelatin staining.Results Naringenin(50 μmol/L)increased signal tansducer and activator of transciption 6(STAT6)phosphorylation and promoted tissue inhibitor of metalloproteinase-3(TIMP-3)expression by 3.1-fold(P＜0.001).After naringenin(80 mg/kg)treatment,compared with the control group,the area of plaque necrotic core in aor-tic root decreased by 53％(P＜0.01),the thickness of fibrous caps increased by nearly 50％(P＜0.05),and the degree of elastic fiber degradation decreased.At the same time,naringenin promoted the expression of TIMP-3 in plaques,and corre-spondingly reduced the activity of MMP in plaques.Lentivirus mediated inhibition of TIMP-3 expression in vivo could reduce the protective effect of naringenin on plaque stability.Conclusion Naringin can increase the expression of TIMP-3 in smooth muscle cells,improve the composition of extracellular matrix,and promote the stability of atherosclerotic plaque.

naringeninsignal tansducer and activator of transcipion 6tissue inhibitor of metalloproteinase-3atherosclerosisplaque stability

何慧、董豆豆、丁萌、朱沅、姜天宇、许晓婷、欧海龙

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贵州医科大学基础医学院生物化学与分子生物学教研室,贵州省贵阳市 561113

柚皮素 信号转导及转录活化因子6 组织型基质金属蛋白酶抑制剂3 动脉粥样硬化 斑块稳定性

国家自然科学基金项目国家自然科学基金项目贵州省科技基金项目

3226023232060219黔科合基础-ZK[2022]重点038

2024

10.20039/j.cnki.1007-3949.2024.07.003

中国动脉硬化杂志
中国病理生理学会 南华大学

中国动脉硬化杂志

CSTPCD
影响因子：1.086
ISSN：1007-3949
年,卷(期)：2024.32(7)