| 杨雅雯,夏敏,吴芬,宋梦星,陆文烨,马占龙.Rho相关卷曲螺旋蛋白激酶1在动脉粥样硬化血管壁中的表达及其与基质金属蛋白酶2及转化生长因子1的相关性[J].中华老年多器官疾病杂志,2023,22(1):53~58 |
| Rho相关卷曲螺旋蛋白激酶1在动脉粥样硬化血管壁中的表达及其与基质金属蛋白酶2及转化生长因子1的相关性 |
| Expression of Rho associated coiled-coil forming protein kinase 1 in mouse arteriosclerotic vessel walls and its correlation with matrix metalloproteinase 2 and transforming growth factor 1 |
| 投稿时间：2022-05-24 |
| DOI：10.11915/j.issn.1671-5403.2023.01.010 |
| 中文关键词: 动脉粥样硬化 Rho相关卷曲螺旋蛋白激酶 基质金属蛋白酶 转化生长因子 心血管事件 |
| 英文关键词:atherosclerosis Rho associated coiled-coil forming protein kinases matrix metalloproteinases transforming growth factor cardiovascular events This work was supported by the General Program of National Natural Science Foundation of China |
| 基金项目:国家自然科学基金面上项目(81971669) |
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| 中文摘要: |
| 目的 研究Rho相关卷曲螺旋蛋白激酶1(ROCK1)在动脉粥样硬化血管壁中的表达及其与基质金属蛋白酶2(MMP2)、转化生长因子1(TGF-β1)的相关性。方法 选择30只载脂蛋白E基因敲除小鼠为实验组,高脂饲料喂养,另选30只C57BL/6小鼠为对照组,普通饲料喂养。在喂养的第10、16、22、28及34周,取眼球血监测小鼠血脂水平；取小鼠腹主动脉作为标本,包埋切片并进行苏木精-伊红染色观察血管壁形态；应用免疫组化染色观察血管壁中ROCK1、MMP2、TGF-β1的表达；使用Image Pro Plus 6.0软件测量切片中血管壁厚度、斑块面积、血管壁中ROCK1、MMP2及TGF-β1的表达量。采用SPSS 27.0统计软件进行数据分析。采用单因素方差分析进行组间比较,两两比较采用Tukey检验。采用Pearson相关与线性回归分析ROCK1与血管壁厚度及斑块面积、MMP2、TGF-β1的关系。结果 成功建立动脉粥样硬化小鼠模型。在喂养第10、16、22、28及34周,实验组血脂水平明显高于对照组,差异有统计学意义(P＜0.05)。自喂养第16周起,实验组小鼠血管内均有斑块形成,随着喂养时间的延长,斑块面积和血管壁厚度不断增加,差异有统计学意义(P＜0.05)；血管壁内ROCK1的表达逐步增高,其表达与斑块面积及血管壁厚度呈正相关(r=0.821,0.730；P＜0.05)。线性相关分析及回归分析显示,ROCK1与MMP2、TGF-β1表达均呈正相关(r=0.801,0.906；P＜0.05)。结论 在动脉粥样硬化血管壁中存在ROCK1蛋白的表达,且表达量随着血管壁厚度增加而增高,ROCK1的表达与MMP2、TGF-β1呈显著正相关性。鉴于ROCK1蛋白的致血管痉挛作用,提示动脉粥样硬化血管壁可能易于痉挛,具体机制需进一步研究。 |
| 英文摘要: |
| Objective To determine the expression of Rho associated coiled-coil forming protein kinase 1 (ROCK1) in atherosclerotic vessel walls and its correlation with matrix metalloproteinase 2 (MMP2) and transforming growth factor 1 (TGF-β1). Methods Thirty apolipoprotein E knockout mice were selected as the experimental group and fed with high-fat diet. Another 30 C57BL/6 mice were selected as the control group and fed with ordinary diet. At the 10th, 16th, 22nd, 28th and 34th weeks of feeding, the eyeball blood samples were harvested to measure the blood lipid levels. The abdominal aorta of mice was collected as samples, and then embedded and sectioned, followed by hematoxylin eosin staining to observe the morphology of vascular wall. Immunohistochemical staining was also performed to observe the expression of ROCK1, MMP2 and TGF-β1 in vascular wall. Image Pro Plus 6.0 software was used to measure the thickness of vascular wall, plaque area, and expression levels of ROCK1, MMP2 and TGF-β1 in vascular wall. SPSS statistics 27.0 was used to analyze the experimental indicators. One-way ANOVA was used to compare among groups, and Tukey test was employed for pairwise comparison. Pearson correlation analysis and linear regression analysis were applied to analyze the relationship of ROCK1 expression with thickness of vascular wall, plaque area and MMP2 and TGF-β1. Results The mouse model of atherosclerosis was successfully established. At the 10th, 16th, 22nd, 28th and 34th weeks of feeding, the blood lipid levels were significantly higher in the experimental group than the control group (P<0.05). Since the 16th week of feeding, plaques were observed in all the blood vessels of the experimental group, and its area and vessel wall thickness were increased with the extension of feeding time (P<0.05). And the expression of ROCK1 in vessel wall was gradually elevated, and the level was positively correlated with plaque area and vessel wall thickness (r=0.821,0.730; P<0.05). Linear correlation analysis and regression analysis showed that the expression of ROCK1 with MMP2 and TGF-β1 were positively correlated (r=0.801,0.906; P<0.05). Conclusion ROCK1 is expressed in atherosclerotic vessel wall, and its expression level is elevated with the thickening of vessel wall and positively correlated with MMP2 and TGF-β1. In view of the vasospasm-causing effect of ROCK1 protein, it is suggested that atherosclerotic vessel walls may be prone to spasm, and the specific mechanism needs further study. |
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