| 从心论治方改善ApoE--/--小鼠动脉粥样硬化及上调ACE2蛋白表达 |
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| 引用本文： | 顾毓艳,蒋 晶,张雅心,陈育尧,陈奕澔,江伟豪,黄志勇,周凤华.从心论治方改善ApoE--/--小鼠动脉粥样硬化及上调ACE2蛋白表达[J].南方医科大学学报,2021,41(11):1623-1630. |
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| 作者姓名： | 顾毓艳 蒋 晶 张雅心 陈育尧 陈奕澔 江伟豪 黄志勇 周凤华 |
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| 作者单位： | 南方医科大学中医药学院,广东 广州 510515;南方医科大学第三附属医院耳鼻喉科,广东 广州 510630 |
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| 基金项目： | 国家自然科学基金;广东省中医药局科研项目 |
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| 摘 要： | 目的 探讨从心论治方（CXLZF）对ApoE-/-小鼠动脉粥样硬化（AS）损伤的作用机制。方法 采用高脂饮食喂养ApoE-/-小鼠12周建立AS模型，随机分为模型组，CXLZF低（4.5 g·kg-1·d-1）、中（9 g·kg-1·d-1）、高（18 g·kg-1·d-1）剂量组，辛伐他汀（5 mg·kg-1·d-1） 组，同时以普通饮食喂养C57BL/6小鼠作为对照组，6只/组。各组小鼠给予相应药物灌胃，对照组、模型组灌胃等体积生理盐水，干预12周。分别采用油红O、Masson、HE染色法观察斑块及肝脏病变情况，检测血脂、血糖及肝功指标；Western blotting法检测血管紧张素转换酶2（ACE2）、E-选择素（E-selectin）蛋白表达，免疫荧光法对ACE2蛋白表达进行定位。在体外，以CXLZF灌胃SD大鼠制作含药血清、生理盐水灌胃大鼠制作对照血清后，采用100 μg/m L ox-LDL干预人脐静脉内皮细胞（HUVECs）建立细胞损伤模型，CXLZF含药血清（5%、10%、20%）干预人脐静脉内皮细胞，对照组、模型组细胞给予10%对照血清。检测细胞ACE2表达。结果 CXLZF低、中、高剂量干预均有效缩小AS小鼠主动脉斑块面积，增加斑块稳定性；同时，CXLZF干预显著降低AS小鼠血清甘油三酯、总胆固醇、低密度脂蛋白胆固醇水平（P<0.05），高剂量组降脂效果最佳；CXLZF干预还可降低AS小鼠血清天门冬氨酸转氨酶和丙氨酸转氨酶含量（P<0.05）、改善肝脏脂肪变性。CXLZF干预显著上调AS小鼠主动脉ACE2、下调E-selectin表达（P<0.05）。细胞实验中，CXLZF含药血清（5%、10%、20%）显著上调氧化低密度脂蛋白干预人脐静脉内皮细胞的ACE2表达（P<0.05）。结论 CXLZF可有效减轻小鼠AS损伤，可能与调控ACE2蛋白有关。
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| 关 键 词： | 从心论治方 动脉粥样硬化 血管紧张素转换酶2 |
Congxin Lunzhi Fang improves aortic atherosclerosis and regulates ACE2 expression in ApoE-/- mice |
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| GU Yuyan,JIANG Jing,ZHANG Yaxin,CHEN Yuyao,CHEN Yihao,JIANG Weihao,HUANG Zhiyong,ZHOU Fenghua.Congxin Lunzhi Fang improves aortic atherosclerosis and regulates ACE2 expression in ApoE-/- mice[J].Journal of Southern Medical University,2021,41(11):1623-1630. |
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| Authors: | GU Yuyan JIANG Jing ZHANG Yaxin CHEN Yuyao CHEN Yihao JIANG Weihao HUANG Zhiyong ZHOU Fenghua |
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| Affiliation: | School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China; Department of Otolaryngology, Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China |
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| Abstract: | Objective To investigate the effect of Congxin Lunzhi Fang (CXLZF) for improving atherosclerosis (AS) and explore its therapeutic mechanism. Methods Thirty ApoE-/- mice were fed on high-fat diet (HFD) to establish AS models, which were randomized equally into model group, low- , medium- and high-dose CXLZF groups (daily dose 4.5, 9, and 18 g/kg, respectively), and simvastatin (5 mg/kg daily) group, with 6 male C57BL/6 mice fed a normal diet as the control group. The mice in the control and model groups were gavaged with normal saline, and those in the treatment groups were gavaged with the indicated drugs for a treatment course of 12 weeks. The changes of atherosclerotic plaque and liver pathologies were observed using oil-red O, HE and Masson staining, and blood lipid profiles and serum levels of glucose, Alanine aminotransferase ( ALT) and Aspartate aminotransferase (AST) of the mice were examined. The protein expressions of ACE2 and E-selectin were determined with Western blotting. Drug-containing serum was collected from SD rats gavaged with CXLZF for treatment of human umbilical vein endothelial cells (HUVECs) with oxidized low-density lipoprotein (ox-LDL)-induced injury, and the protein expression of ACE2 in the cells was determined. Results In ApoE-/- mice, CXLZF at all the 3 doses significantly reduced the plaque area and increased the collagen content in atherosclerotic plaque, indicating improved plaque stability. CXLZF treatment, especially at the high dose, also significantly reduced the levels of serum lipids (P<0.05). CXLZF significantly lowered serum ALT and AST levels, mitigated hepatocyte steatosis (P<0.05), increased the protein expression of ACE2 and down-regulated E-selectin expression (P<0.05) in the mice. In HUVEC cultures, CXLZF-containing serum (5%, 10%, and 20%) significantly up-regulated the cellular expression of ACE2 protein (P<0.05). Conclusion CXLZF relieves aortic atherosclerosis in ApoE-/- mice possibly by regulating ACE2 protein. |
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| Keywords: | Congxin Lunzhi Fang arotic atherosclerosis angiotensin-converting enzyme 2 |
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