血管平滑肌细胞凋亡与尿毒症血管钙化  

Relationship between vascular smooth muscle cell apoptosis and uremic vascular calcification

作　　者：刘书馨[1] 常明[1] 刘红[1] 王志宏[1] 刘焱[1] 藤兰波[1] 赵华[1] 

机构地区：[1]辽宁省大连市中心医院肾内科,116033

出　　处：《中华肾脏病杂志》2007年第6期362-365,共4页Chinese Journal of Nephrology

基　　金：大连市卫生局资助（2005-150）

摘　　要：目的探讨尿毒症患者血管平滑肌细胞（VSMC）捌亡与血管钙化之间的关系及其与临床指标的相关性。方法在43例尿毒症患者行动-静脉内瘘手术时留取桡动脉0．5～1cm。用茜素红染色判断血管中膜钙化,并根据茜素红染色结果将患者分为钙化组和无钙化组。以肾功能正常、年龄相匹配的因外周血管疾病行血管手术的4例患者的动脉为对照组。采用DNA片段原位缺口末端标记技术（TUNEL法）检测上述3组血管平滑肌细胞凋亡情况,结果用凋亡指数表示。用免疫组化的方法检测凋亡相关基囚p53、Bcl-2的表达情况。临床指标包括血钙、血磷、钙磷乘积、全段甲状旁腺素（iPTH）、血浆白蛋白（Alb）、血红蛋白（Hb）、总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白（LDL）、C反应蛋白（CRP）、丙二醛（MDA）、超氧化物歧化酶（SOD）。用Pearson相关分析计算凋亡指数与上述临床指标的相关性。结果尿毒症患者的血管中膜均可见到明显的VSMC凋亡,钙化组VSMC凋亡指数显著高于无钙化组（48．13±17．81比15．90±8．25,P＜0．01）。而在对照组血管中膜只有极少量凋亡的VSMC。钙化组p53表达比无钙化组和对照组明显升高（31．22±14．25比20．67±7．35、4．17±2．61．P＜0．01）,Bcl-2表达比对照组明显降低（4．29±2．16比14．87±5．62,P＜0．01）。VSMC凋亡指数与临床指标中的钙磷乘积、血磷和LDL水平呈正相关（P＜0．05）。结论尿毒症患者桡动脉中膜存在VSMC凋亡,且VSMC凋亡发生在血管钙化之前。VSMC凋亡可能参与了尿毒症患者血管钙化的发生和发展。Objective To explore the relationship between vascular smooth muscle cell （VSMC） apoptosis and uremic vascular calcification, Methods Pieces of radial artery were taken from 43 uremic patients at the time of internal arteriovenous fistula operation. Alizarin red staining was used to determine medial layer vascular calcification, Uremic patients were divided into two groups according to the results of calcification stain. Pieces of radial artery from age-matched normal renal function patients with periarteriole diseases were used as control. Apoptosis of VSMC was detected by terminal deoxynucleotidyl transferease-mediated biotinylated deoxyuridine triphosphate nick end labeling （TUNEL） and apoptosis index （AI） was calculated. Expressive levels of apoptosis-associated genes p53 and Bcl-2 were examined by immunohistochemistry. Related clinical and laboratory parameters were determined as well. Results Obvious VSMC apoptosis in medial layer of uremic patients＇ radial artery was noticed both in calcification positive and negative groups. AI of the calcification positive group was significant higher than that of negative group （48.13±17.81 vs 19.50±8,25,P〈0.01）. There was little VSMC apoptosis in control group. The expression of Bcl-2 in calcification positive group was markedly decreased compared to control group （4.29 ±2.16 vs 14.87 ±5.62） while the expression of p53 was markedly increased in calcification positive group compared to the other two groups （31.22±14.25 vs 20.67±7.35, 4.17± 2.61, P〈0.01）. AI was positively correlated to product of serum calcium and phosphorus, and the levels of serum phosphorus and LDL （P〈0.05）. Conclusions There is VSMC apoptosis in the medial layer of uremic patients＇ radial artery. VSMC apoptosis occurs before overt artery calcification and it is more severe in calcification positive artery, which suggests that VSMC apoptosis takes part in the pathogenesis and development of vascular calcification in uremic patients. Managements lowering th

关 键 词：尿毒症 肌细胞 平滑肌 钙质沉着症 凋亡 

分 类 号：R686[医药卫生—骨科学]