尿毒症患者血浆蛋白酶体与内皮功能损伤的相关性

目的 探讨尿毒症患者血浆蛋白酶体与动脉内皮损伤的相关性。方法 选择新诊断未透析的尿毒症患者（A组，45例）和已行血液透析6~12个月的尿毒症患者（透析充分为B组，44例；透析不充分为C组，31例）为对象。正常健康人15例为健康对照组（D组）。应用多普勒超声检测左前臂桡动脉内-中膜厚度和内皮舒张功能。酶联免疫法（ELISA）检测各组血浆20S蛋白酶体、肿瘤坏死因子α（TNF-α）、C-反应蛋白（CRP）和转化生长因子β1（TGF-β1）的含量。分光光度法检测血浆20S蛋白酶体的活性。 结果 D组血浆20S蛋白酶体含量和活性均极低。与D组比较，A组、B组和C组患者血浆20S蛋白酶体含量和活性，以及TNF-α、CRP和TGF-β1的含量均显著升高。与A组比较，B组血浆20S蛋白酶体含量和活性均显著降低，而C组明显升高；TNF-α、CRP和TGF-β1也存在相似的变化。与D组比较，A组、B组和C组患者桡动脉内皮依赖性舒张功能（EDD）和非依赖性舒张功能（EID）均显著下降；切面内膜中膜面积（IMA）均显著增加；C组患者桡动脉内-中膜厚度（IMT）明显增厚，腔内径明显变小。与A、B组比较，C组患者EDD进一步显著降低。与D组血清比较，A、B、C组血清刺激内皮细胞释放蛋白酶体和TNF-α均显著升高，尤以C组升高最明显。在A组和C组，血浆20S蛋白酶体含量和活性、炎性细胞因子与内皮舒张功能EDD均呈负相关；血浆20S蛋白酶体含量和活性与TNF-α、CRP和TGF-β1均呈正相关。 结论 尿毒症患者血浆20S蛋白酶体含量和活性的显著升高与动脉内皮功能损伤密切相关。

Correlation between serum proteasome and endothelial dysfunction in patients with uremia

Objective To investigate the correlation between plasma proteasome and endothelial dysfunction in patients with uremia. Methods Forty-five uremic patients who did not receive hemodialysis were defined as A group; seventy-five uremic patients who had received hemodialysis for 6 to 12 months were divided into sufficient hemodialysis group (44 cases, B group) and insufficient hemodialysis group (31 cases, C group). The primary disease of these patients was chronic glomerulonephritis. Fifteen healthy people were defined as healthy control group (D group). The diameter of radial artery lumen (DRL), intima-media thickness (IMT), intima-media area (IMA), endothelium-dependent or independent dilation (EDD or EID) of radial artery in right forearm were detected by diasonography. The levels of 20S proteasome, tumor necrosis factor α（TNF-α）, C-reaction protein (CRP) and transforming growth factor β 1 (TGF-β1) of plasma and supernatant of cultured human umbilical veins endothelium (HUVEC) were determined by enzyme linked immunosorbent assay (ELISA). 20S proteasome activity was analyzed by special substrate. Results Compared with D group, the level and activity of 20S proteasome, as well as TNF-α, CRP and TGF-β1 in A, B and C groups were significantly increased. Compared with A group, these plasma indices levels were significantly decreased in B group but strongly increased in C group. IMT and IMA were elevated, while DRL, EDD and EID were decreased significantly in A, B and C groups when compared with D group. These parameters were worse in C group than those in A and B groups. After co-culture of HUVEC with above mentioned human uremic serum, the level and activity of 20S proteasome and TNF-α were higher in A, B, C groups than that in D group. In A and C groups, there were negative correlations of EDD with the level or activity of 20S proteasome, TNF-α, CRP and TGF-β1, and there were positive correlations of 20S proteasome level or activity with TNF-α, CRP and TGF-β1. Conclusions 20S proteasome level and activity are significantly increased in uremic patients. There is a close correlation between 20S proteasome and endothelial dysfunction of radial artery.