肌腱蛋白C和肌腱蛋白X与转化生长因子β1与合成型血管平滑肌细胞在动脉粥样硬化斑块纤维化过程中关系的实验研究  

Study of the relationship between the expression of Tenascin C,X,transforming growth factor-β1 and synthetic vascular smooth muscle cells in the process of atherosclerosis plaque fibrosis

作　　者：夏敏 吴芬 陆文烨 宋梦星 马占龙[1] XIA Min;WU Fen;LU Wen-ye;SONG Meng-xing;MA Zhan-long(Department of Radiology,First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China)

机构地区：[1]南京医科大学第一附属医院放射科,210029

出　　处：《中国心血管病研究》2022年第9期828-833,共6页Chinese Journal of Cardiovascular Research

基　　金：国家自然科学基金面上项目(81971669)。

摘　　要：目的 研究小鼠动脉粥样硬化模型斑块形成过程中肌腱蛋白C(TNC)、肌腱蛋白X(TNX)及转化生长因子β1(TGF-β1)与合成型血管平滑肌细胞(VSMC)表达及斑块纤维化的关系。方法 选择雄性APOE-/-小鼠25只为实验组,高脂饲料喂养;另选择雄性野生型C57BL/6小鼠25只为对照组,普通饲料喂养,两组小鼠分别于喂养10、16、22、28、34周各取5只腹主动脉进行HE染色观察斑块形成情况,免疫组化染色法定量测定斑块TNC、TNX、TGF-β1与原肌球蛋白4(TPM4)阳性表达区的总面积及相对灰度值,masson染色观察斑块胶原纤维形成情况。结果 实验组小鼠自16周起,腹主动脉有斑块形成,并且随高脂饲料喂养时间延长,斑块面积逐渐增大,斑块内TNC、TNX、TGF-β1、TPM4及胶原纤维表达随着喂养时间延长逐渐增加,16周、22周、28周、34周TNC的平均光密度值为(0.013±0.007)、(0.028±0.002)、(0.039±0.010)、(0.065±0.002),TNX的平均光密度值分别为(0.002±0.001)、(0.007±0.002)、(0.010±0.001)、(0.016±0.005),TGF-β1的平均光密度值分别为0.018±0.006、0.029±0.003、0.035±0.001、0.042±0.002,TPM4的平均光密度值分别为0.016±0.011、0.019±0.002、0.026±0.005、0.050±0.013,差异均有统计学意义(P<0.05)。TNC与TPM4、TNX与TPM4、TGF-β1与TPM4表达均呈正相关性及一致性,TNC/TPM4(R~2=0.640,P<0.05),TNX/TPM4(R~2=0.674,P<0.05),TGF-β1/TPM4(R~2=0.404,P<0.05)。结论 在动脉粥样硬化斑块形成过程中,随着斑块面积的增大,TNC、TNX、TGF-β1及合成型VSMC标记蛋白TPM4的表达逐渐增加,主要分布于胶原纤维表达区域,并且具有正相关性及一致性,证明TNC、TNX、TGF-β1及合成型VSMC可能存在协同正性调控动脉粥样硬化纤维斑块形成及进展的关系。Objective To observe the relationship between the expression of Tenascin-C(TNC),TenascinX(TNX) and transforming growth factor β1(TGF β1) and synthetic vascular smooth muscle cells(VSMC) during the formation of aortic atherosclerotic plaque in mice fed with long-term high-fat diet.Methods 25 male APOE-/-mice were selected as the experimental group and fed with high fat diet.25 male wild type C57BL/6 mice were selected as the control group and fed with normal diet.Five abdominal aortas of the two groups were taken for HE staining at 10,16,22,28 and 34 weeks respectively to observe the plaque formation.The total area and relative gray value of TNC,TNX,TGF-β1 and TPM4 positive expression areas of plaques were quantitatively determined by immunohistochemical staining,and the formation of collagen fibers in plaques was observed by masson staining.Results Plaques in the abdominal aorta of mice in the experimental group have been formed at the 16 th week,and as plaque area increased with the prolongation of feeding time,the expression of TNC,TNX,TGF-β1,TPM4 and collagen fibers in plaque gradually increased.The average optical density of TNC points at 16 week,22 week,28 week,34 week was(0.013 ± 0.007),(0.028 ± 0.002),(0.039 ± 0.010) and(0.065 ± 0.002);the average optical density of TNX at different time points was(0.002±0.001),(0.007±0.002),(0.010±0.001) and(0.016±0.005);the average optical density of TGF-β1 at different time points was(0.018±0.006),(0.029±0.003),(0.035±0.001) and(0.042 ± 0.002);the average optical density of TPM4 at different time points was(0.016 ± 0.011),(0.019 ± 0.002),(0.026±0.005) and(0.050±0.013);and the differences were statistically significant(P<0.05).There was a positive correlation between the expression of TNC and TPM4,TNX and TPM4,TGF-β1 and TPM4,TNC/TPM4(R~2=0.640,P<0.05),TNX/TPM4(R~2=0.674,P<0.05),TGF-β1/TPM4(R~2=0.404,P<0.05).Conclusion In the process of atherosclerotic plaque formation,the expression of TNC,TNX,TGF-β1 and TPM4 increases gradually with the increase

关 键 词：动脉粥样硬化 肌腱蛋白C 肌腱蛋白X 转化生长因子Β1 合成型血管平滑肌细胞 

分 类 号：R95-33[医药卫生—药学] R541.4