摘要
目的观察微炎性反应对血管钙化（VC）的影响，并探讨低密度脂蛋白受体（LDIJr）途径失调在炎性反应致VC中的作用机制。方法28例行动静脉内瘘手术的血液透析（HD）患者被纳入研究，根据血清C反应蛋白（CRP）水平分为对照组（n=14）和炎性反应组（n=14）。取材动静脉内瘘手术时部分切除的桡动脉组织，于4％甲醛固定或OCT包埋分别制作石蜡切片和冰冻切片。采用HE及茜素红染色观察泡沫细胞形成及钙化沉积情况；免疫组化及免疫荧光染色检测VC相关蛋白表达，如骨形成蛋白2（BMP-2）、胶原I、碱性磷酸酶（ALP）；并同时检测LDLr及其转录调节相关核因子的表达，如类固醇调节元件结合蛋白2（SREBP-2）及SREBP裂解激活蛋白（SCAP）。结果两组患者在年龄、体质量、血红蛋白、总蛋白及白蛋白、血脂谱、钙磷乘积及甲状旁腺激素等差异均无统计学意义。HE染色及茜素红染色证实，炎性反应组患者桡动脉组织内可见大量泡沫细胞形成和钙化沉积。免疫组化及免疫荧光染色显示，与对照组比较，炎性反应组患者桡动脉组织BMP-2、胶原I、ALP表达增加，α-SMA表达减少，LDLr、SREBP-2表达及SCAP由内质网向高尔基体的转位显著增加。进一步分析显示，炎性反应组LDLr表达与BMP-2（r=0．782，P〈0．01）及胶原I（r=0．644，P〈0．05）表达呈正相关。结论炎性反应促进HD患者VC，部分机制可能与其诱导LDLr负反馈途径失调相关。
Objective To investigate whether low density lipoprotein receptor （LDLr） pathway involves in the progression of vascular calcification （VC） in hemodialysis patients under microinflammation. Methods Twenty-eight hemodialysis patients were divided into control and inflammation group according to plasma C-reactive protein level. Surgically removed tissues from radial artery of patients receiving arteriovenostomy were used in experiments. Foam cell formation and calcification deposition were observed by hematoxylin-eosin （HE） and alizarin red S staining respectively. VC-related protein expression, such as bone morphogenetic proteins-2 （BMP-2）, collagen I , alkaline phosphatase （ALP）, and LDLr and its related nuclear factor of transcriptional regulation, such as sterol regulatory element binding protein-2 （SREBP-2） and SREBP cleavage- activating protein （SCAP）, were detected by immunohistochemistry and immunofluorescence staining.Results HE and alizarin red S staining showed that there were parallel increased foam cell formation and calcium deposit in continuous cross-sections of radial arteries in inflammation group compared to control group, which were closely correlated with increased protein expressions of LDLr, SREBP-2, BMP-2, and collagen I as shown by immunohistochemical and immunofluorescent staining. Confocal microscopy confirmed that inflammation enhanced the translocation of SCAP/ SREBP-2 complex from endoplasmic reticulum to Golgi, thereby activating LDLr gene transcription. Inflammation increased protein expression of ALP and reduced protein expression of alpha-smooth muscle actin, contributing to the phenotype conversion of vascular smooth muscle cells in calcified vessels from the fibroblastic to the osteogenic, which were the main cell components in VC. Further analysis showed that the disruption of LDLr pathway induced by inflammation was positively correlated with the enhanced expression of BMP-2 and collagen I （r=0.782, P〈0.01; r=0.644, P〈 0.05）. Conclusion Inflammation accelerates the progression of VC in hemodialysis patients through the disruption of LDLr feedback regulation.
出处
《中华肾脏病杂志》
CAS
CSCD
北大核心
2012年第8期592-596,共5页
Chinese Journal of Nephrology
基金
国家自然科学基金（81070571）
江苏省自然科学基金（BK2009279）
关键词
炎症
钙质沉着症
受体
LDL
血液透析
血管钙化
Inflammation
Caleinosis
Receptors, LDL
Hemodialysis
Vascular calcification
