中华肾脏病杂志
中華腎髒病雜誌
중화신장병잡지
2012年
5期
371-376
,共6页
罗志锋%冯冰%曾薇%郭艳红%庞琦%陈吉刚%牟娇%李燕%聂凌%袁发焕%冯兵
囉誌鋒%馮冰%曾薇%郭豔紅%龐琦%陳吉剛%牟嬌%李燕%聶凌%袁髮煥%馮兵
라지봉%풍빙%증미%곽염홍%방기%진길강%모교%리연%섭릉%원발환%풍병
尿毒症%动脉粥样硬化%蛋白酶体%内皮功能
尿毒癥%動脈粥樣硬化%蛋白酶體%內皮功能
뇨독증%동맥죽양경화%단백매체%내피공능
Uremia%Atherosclerosis%Proteasome%Inflammation
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(EHSA)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.
目的 探討尿毒癥患者血漿蛋白酶體與動脈內皮損傷的相關性.方法 選擇新診斷未透析的尿毒癥患者(A組,45例)和已行血液透析6～12箇月的尿毒癥患者(透析充分為B組,44例；透析不充分為C組,31例)為對象.正常健康人15例為健康對照組(D組).應用多普勒超聲檢測左前臂橈動脈內-中膜厚度和內皮舒張功能.酶聯免疫法(EHSA)檢測各組血漿20S蛋白酶體、腫瘤壞死因子α(TNF-α)、C-反應蛋白(CRP)和轉化生長因子β1(TGF-β1)的含量.分光光度法檢測血漿20S蛋白酶體的活性.結果 D組血漿20S蛋白酶體含量和活性均極低.與D組比較,A組、B組和C組患者血漿20S蛋白酶體含量和活性,以及TNF-α、CRP和TGF-β1的含量均顯著升高.與A組比較,B組血漿20S蛋白酶體含量和活性均顯著降低,而C組明顯升高；TNF-α、CRP和TGF-β1也存在相似的變化.與D組比較,A組、B組和C組患者橈動脈內皮依賴性舒張功能( EDD)和非依賴性舒張功能(EID)均顯著下降；切麵內膜中膜麵積(IMA)均顯著增加；C組患者橈動脈內-中膜厚度(IMT)明顯增厚,腔內徑明顯變小.與A、B組比較,C組患者EDD進一步顯著降低.與D組血清比較,A、B、C組血清刺激內皮細胞釋放蛋白酶體和TNF-α均顯著升高,尤以C組升高最明顯.在A組和C組,血漿20S蛋白酶體含量和活性、炎性細胞因子與內皮舒張功能EDD均呈負相關；血漿20S蛋白酶體含量和活性與TNF-α、CRP和TGF-β1均呈正相關.結論 尿毒癥患者血漿20S蛋白酶體含量和活性的顯著升高與動脈內皮功能損傷密切相關.
목적 탐토뇨독증환자혈장단백매체여동맥내피손상적상관성.방법 선택신진단미투석적뇨독증환자(A조,45례)화이행혈액투석6～12개월적뇨독증환자(투석충분위B조,44례；투석불충분위C조,31례)위대상.정상건강인15례위건강대조조(D조).응용다보륵초성검측좌전비뇨동맥내-중막후도화내피서장공능.매련면역법(EHSA)검측각조혈장20S단백매체、종류배사인자α(TNF-α)、C-반응단백(CRP)화전화생장인자β1(TGF-β1)적함량.분광광도법검측혈장20S단백매체적활성.결과 D조혈장20S단백매체함량화활성균겁저.여D조비교,A조、B조화C조환자혈장20S단백매체함량화활성,이급TNF-α、CRP화TGF-β1적함량균현저승고.여A조비교,B조혈장20S단백매체함량화활성균현저강저,이C조명현승고；TNF-α、CRP화TGF-β1야존재상사적변화.여D조비교,A조、B조화C조환자뇨동맥내피의뢰성서장공능( EDD)화비의뢰성서장공능(EID)균현저하강；절면내막중막면적(IMA)균현저증가；C조환자뇨동맥내-중막후도(IMT)명현증후,강내경명현변소.여A、B조비교,C조환자EDD진일보현저강저.여D조혈청비교,A、B、C조혈청자격내피세포석방단백매체화TNF-α균현저승고,우이C조승고최명현.재A조화C조,혈장20S단백매체함량화활성、염성세포인자여내피서장공능EDD균정부상관；혈장20S단백매체함량화활성여TNF-α、CRP화TGF-β1균정정상관.결론 뇨독증환자혈장20S단백매체함량화활성적현저승고여동맥내피공능손상밀절상관.
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.
