| 摘要: |
| 目的 探讨RAS阻滞剂及LCZ696对动脉粥样硬化小鼠血管紧张素转换酶2-血管紧张素-(1-7)- Mas轴[ACE2-Ang-(1-7)-Mas轴]的影响及可能的机制。 方法 采用6周龄健康雄性ApoE-/-小鼠28只和C57BL/6小鼠7只。ApoE-/-小鼠高脂喂养建模后随机分为4组，分别予以生理盐水、依那普利、缬沙坦和LCZ696灌胃处理，C57BL/6小鼠予以等量生理盐水灌胃。药物干预6周后处死取血样及病理标本，应用全自动生化分析仪测定各组血清中低密度脂蛋白胆固醇（LDL-C）、总胆固醇（TC）水平，ELISA法测定血清C反应蛋白（CRP）、白介素-6（IL-6）、ACE2、Ang-(1-7)、血管紧张素II（AngII）水平，油红O染色法测斑块脂质含量，RT-qPCR法测定主动脉ACE2mRNA表达，免疫组化法测定主动脉斑块中ACE2、Ang-(1-7)蛋白表达。 结果 与C57BL/6组相比，ApoE-/-对照组LDL-C、TC、CRP、IL-6水平升高（P<0.01），主动脉斑块明显增加（P<0.01）。与ApoE-/-对照组相比，依那普利组、缬沙坦组和LCZ696组LDL-C、TC水平差异无统计学意义（P>0.05），依那普利组、缬沙坦组和LCZ696组血清CRP、IL-6、AngII水平显著降低（P<0.01），ACE2、Ang-(1-7)水平显著升高（P<0.01），依那普利组、缬沙坦组和LCZ696组斑块显著减少（P<0.01），依那普利组和LCZ696组的主动脉中ACE2mRNA表达增加（P<0.01，P<0.05），依那普利组、缬沙坦组和LCZ696组主动脉斑块中ACE2和Ang-(1-7)蛋白表达增加（P<0.01）。与依那普利组、缬沙坦组相比，LCZ696组斑块减少更明显（P<0.05），主动脉斑块中ACE2和Ang-(1-7)蛋白表达增加更明显（P<0.01，P<0.05）。 结论 依那普利、缬沙坦和LCZ696均可以通过ACE2- Ang-(1-7)-Mas轴来抑制动脉粥样硬化的发展，且LCZ696抗动脉粥样硬化作用更明显。 |
| 关键词: 动脉粥样硬化 RAS阻滞剂 LCZ696 血管紧张素转换酶2 血管紧张素-(1-7) |
| DOI： |
| 分类号: |
| 基金项目:宁波市自然科学基金项目（2017A610197） |
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| Effect of RAS blockers and LCZ696 on ACE2-Ang-(1-7) -Mas axis in atherosclerotic mice |
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xiedonglin1, daiting1, huangli1, maiyifeng1, jiangjun2, xieyanqing1, hewenming1
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1.the Affiliated Hospital of Medical School of Ningbo University School;2.the Second Affiliated Hospital of Zhejiang University School of Medicine
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| Abstract: |
| objective To investigate the effect of RAS blockers and LCZ696 on angiotensin converting enzyme 2- angiotensin-(1-7) -Mas axis[ACE2-Ang-(1-7) -Mas axis] in atherosclerotic mice and the possible mechanism. Methods 28 healthy male ApoE-/- mice which aged 6 weeks and 7 C57BL/6 mice were used. ApoE-/- mice were randomly divided into 4 groups after the modeling of high-fat feeding, and were treated with saline, Enalapril, Valsartan and LCZ696 respectively. C57BL/6 mice were given equal amount of saline. After six-week Drug intervention，we collect blood samples and pathological specimens. Then, Serum levels of low density lipoprotein cholesterol (LDL-C), Total Cholesterol (TC) were measured by automatic biochemical analyzer, Serum levels of C reactive protein (CRP)，interleukin-6 (IL-6)，ACE2, Ang- (1-7)，angiotensin II(AngII )were determined by ELISA , the lipid content of plaque was measured by Oil Red O staining ,the expression of aortic ACE2 mRNA was determined by RT-qPCR and the expression of ACE2, Ang-(1-7) proteins in aortic plaques was determined by immunohistochemistry. Results Compared with C57BL/6 group, LDL-C，TC，CRP and IL-6 levels of ApoE-/- control group were increased (P<0.01) and aortic plaque was significantly increased (P<0.01) as well. Compared with ApoE-/- control group, there was no significant difference in LDL-C and TC levels between the enalapril group, valsartan group and LCZ696 group (P>0.05). In addition, serum CRP，IL-6 and AngII levels of Enalapril group, Valsartan group and LCZ696 group were decreased(P<0.01) and serum ACE2, Ang-(1-7) levels were significantly increased (P<0.01). Moreover, the plaque of Enalapril group, valsartan group and LCZ696 were significantly reduced (P<0.01), ACE2 mRNA expression increased in the aorta of enalapril group and LCZ696 group (P<0.01, P<0.05), and ACE2, Ang-(1-7) protein expression increased in aortic plaques of enalapril group, valsartan group and LCZ696 group (P<0.01). Compared with enalapril group and valsartan group, the reduction of aorta plaque was more significant in the LCZ696 group (P<0.05) and the expression of ACE2 and Ang-(1-7) protein in the aortic plaque increased more (P<0.01, P<0.05). Conclusion Enalapril, valsartan and LCZ696 can all inhibit the development of atherosclerosis through ACE2-Ang-(1-7)-Mas axis, and LCZ696 has more obvious anti-atherosclerosis effect. |
| Key words: atherosclerosis RAS inhibitor LCZ696 ACE2 Ang-(1-7) |