尿毒症患者桡动脉钙化与平滑肌肌动蛋白α及骨桥蛋白表达关系的研究
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国家自然科学基金资助(30070352,30700368),江苏省自然科学基金青年科技创新启动基金资助(BK2007609),江苏省卫生厅"135"重点学科科研基金资助


Calcification of radial arteries from uremia patients and its relationship with vascular smooth muscle cells transformation
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    摘要:

    目的:观察30例尿毒症患者桡动脉钙化的组织学特点并分析可能的机制-方法:用硝酸银染色和茜素红染色了解血管钙化的情况,免疫组化研究平滑肌肌动蛋白α(α-SMA)和骨桥蛋白(OP)的表达特点,并在体外高钙磷的培养条件下,观察大鼠血管平滑肌细胞上述指标的变化-结果:11例尿毒症患者出现桡动脉钙化,主要局限于血管中层,与血钙磷乘积水平升高密切相关-平滑肌层α-SMA表达明显减弱,轻/中度钙化组为71.11% ± 4.93%,重度钙化组为54.66% ± 5.15%,与无钙化组(89.54% ± 2.92%)相比有显著性差异(P < 0.01);钙化的血管平滑肌细胞中骨桥蛋白的含量亦明显增加(轻/中度钙化组为22.19% ± 7.12%,重度钙化组为37.87% ± 6.17%),显著高于无钙化组(6.85% ± 6.19%,P < 0.01)-当用高钙磷的营养液培养10天后,血管平滑肌细胞间出现钙盐沉积,OP蛋白的含量明显增加,伴α-SMA表达减少-结论:尿毒症患者的血管钙化以中层为主,高钙磷乘积的环境可诱导血管平滑肌细胞α-SMA的表达明显减少-OP含量增多,表现出类似成骨样细胞的生物学特点-

    Abstract:

    Objective:To analysis the feature of vascular calcification in the radial arteries from 30 uremia patients,observe the effect of high calcium and high phosphate enviroment on rat vascular smooth muscle cells(VSMCs) in vitro. Methods:Radial arteries from uremia patients were examined for calcification by von Kossa and Alizarin red staining. Expression of smooth muscle cells marker α-SMA and bone matrix protein OP were detected by immunohistochemistry. Rat VSMCs were cultured in high calcium/high phosphate medium for 10 days to detect calcium deposition,furthermore, expression of α-SMA and OP was analyzed by Western blot. Results:Radial artery calcification mainly located in the medial layer,which occurred in 11 uremia patients. Immunohistochemistry staining revealed that in the mild/moderate calcified arteries group,expression of α-SMA was 71.11% ± 4.93% and in severe calcification group was 54.66% ± 5.15%,significantly lower than that of none calcification group(89.54% ± 2.92%,P < 0.01). Furthermore,the content of bone matrix protein OP was also upregulated in the uremia arteries,in mild/moderate calcification group was 22.19% ± 7.12% and in severe calcification group was 37.87% ± 6.17%(compared with none calcification group,6.85% ± 6.19%,P < 0.01). Calcium deposition was observed in VSMCs cultured with high calcium/high phosphate medium for 10 days,and production of OP was increased,expression of α-SMA was decreased. Conclusion:Calcificated vascular from uremia patients displayed decreased expression of α-SMA and upregulation of OP protein in the media layer,which was correlated with high calcium plus phosphate product,indicating that VSMCs showed the feature of osteoblast-like cells.

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王宁宁,杨俊伟,俞香宝,胡建明,邢昌赢,彭 韬,钱 军,王笑云.尿毒症患者桡动脉钙化与平滑肌肌动蛋白α及骨桥蛋白表达关系的研究[J].南京医科大学学报(自然科学版),2008,28(11):1369-1373

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  • 收稿日期:2008-05-22
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