中华肾脏病杂志
中華腎髒病雜誌
중화신장병잡지
2014年
8期
614-618
,共5页
于亚民%贾俊亚%闫铁昆%高姗%商文雅%韦丽%李红芬%林珊
于亞民%賈俊亞%閆鐵昆%高姍%商文雅%韋麗%李紅芬%林珊
우아민%가준아%염철곤%고산%상문아%위려%리홍분%림산
尿毒症%NF-κB%血管钙化%吡咯烷二硫代甲酸铵
尿毒癥%NF-κB%血管鈣化%吡咯烷二硫代甲痠銨
뇨독증%NF-κB%혈관개화%필각완이류대갑산안
Uremia%NF-κB%Vascular calcification%Pyrrolidine-dithio-carbamate ammonium
目的 探讨NF-κB抑制剂吡咯烷二硫代甲酸铵(PDTC)对尿毒症大鼠主动脉钙化的干预作用及相关机制.方法 16只雄性SD大鼠被随机分为尿毒症模型组及PDTC干预组,均予0.75％腺嘌呤及高磷(1％)饮食,制备尿毒症动脉钙化模型,干预组同时腹腔注射PDTC 100 rmg· kg-1·d..另取8只匹配大鼠作为健康对照.8周后处死大鼠,HE及yon Kossa染色观察腹主动脉病理改变及钙化情况,免疫组织化学方法检测骨调素(OPN)、核心结合因子α1(Cbfα1)在主动脉的定位与表达,Western印迹检测主动脉NF-κB总p65与细胞核内p-p65、OPN、Cbfo1等蛋白表达量.结果 造模4周及8周,尿毒症组、PDTC组大鼠血清BUN、Scr、血磷、钙磷乘积均显著高于对照组(均P＜ 0.01),但此两组间差异无统计学意义(P＞0.05);造模8周,尿毒症组和PDTC组大鼠主动脉明显增厚及中膜钙化,PDTC组程度较轻(P＜0.05),免疫组化显示主动脉内皮下、中膜及外膜均有OPN、Cbfα1表达,PDTC组表达量较少(均P＜0.05);Western印迹显示PDTC组主动脉NF-κB总p65、核p-p65、OPN、Cbfα1表达均较尿毒症组下降(均P＜ 0.01),且Cbfα1表达与p65、核p-p65表达呈正相关(r=0.707,P＜0.01;r=0.507,P＜0.01).结论 PDTC可阻断NF-κB p65核转位,抑制尿毒症大鼠主动脉Cbfα1表达,减轻血管钙化.
目的 探討NF-κB抑製劑吡咯烷二硫代甲痠銨(PDTC)對尿毒癥大鼠主動脈鈣化的榦預作用及相關機製.方法 16隻雄性SD大鼠被隨機分為尿毒癥模型組及PDTC榦預組,均予0.75％腺嘌呤及高燐(1％)飲食,製備尿毒癥動脈鈣化模型,榦預組同時腹腔註射PDTC 100 rmg· kg-1·d..另取8隻匹配大鼠作為健康對照.8週後處死大鼠,HE及yon Kossa染色觀察腹主動脈病理改變及鈣化情況,免疫組織化學方法檢測骨調素(OPN)、覈心結閤因子α1(Cbfα1)在主動脈的定位與錶達,Western印跡檢測主動脈NF-κB總p65與細胞覈內p-p65、OPN、Cbfo1等蛋白錶達量.結果 造模4週及8週,尿毒癥組、PDTC組大鼠血清BUN、Scr、血燐、鈣燐乘積均顯著高于對照組(均P＜ 0.01),但此兩組間差異無統計學意義(P＞0.05);造模8週,尿毒癥組和PDTC組大鼠主動脈明顯增厚及中膜鈣化,PDTC組程度較輕(P＜0.05),免疫組化顯示主動脈內皮下、中膜及外膜均有OPN、Cbfα1錶達,PDTC組錶達量較少(均P＜0.05);Western印跡顯示PDTC組主動脈NF-κB總p65、覈p-p65、OPN、Cbfα1錶達均較尿毒癥組下降(均P＜ 0.01),且Cbfα1錶達與p65、覈p-p65錶達呈正相關(r=0.707,P＜0.01;r=0.507,P＜0.01).結論 PDTC可阻斷NF-κB p65覈轉位,抑製尿毒癥大鼠主動脈Cbfα1錶達,減輕血管鈣化.
목적 탐토NF-κB억제제필각완이류대갑산안(PDTC)대뇨독증대서주동맥개화적간예작용급상관궤제.방법 16지웅성SD대서피수궤분위뇨독증모형조급PDTC간예조,균여0.75％선표령급고린(1％)음식,제비뇨독증동맥개화모형,간예조동시복강주사PDTC 100 rmg· kg-1·d..령취8지필배대서작위건강대조.8주후처사대서,HE급yon Kossa염색관찰복주동맥병리개변급개화정황,면역조직화학방법검측골조소(OPN)、핵심결합인자α1(Cbfα1)재주동맥적정위여표체,Western인적검측주동맥NF-κB총p65여세포핵내p-p65、OPN、Cbfo1등단백표체량.결과 조모4주급8주,뇨독증조、PDTC조대서혈청BUN、Scr、혈린、개린승적균현저고우대조조(균P＜ 0.01),단차량조간차이무통계학의의(P＞0.05);조모8주,뇨독증조화PDTC조대서주동맥명현증후급중막개화,PDTC조정도교경(P＜0.05),면역조화현시주동맥내피하、중막급외막균유OPN、Cbfα1표체,PDTC조표체량교소(균P＜0.05);Western인적현시PDTC조주동맥NF-κB총p65、핵p-p65、OPN、Cbfα1표체균교뇨독증조하강(균P＜ 0.01),차Cbfα1표체여p65、핵p-p65표체정정상관(r=0.707,P＜0.01;r=0.507,P＜0.01).결론 PDTC가조단NF-κB p65핵전위,억제뇨독증대서주동맥Cbfα1표체,감경혈관개화.
Objective To investigate the effects of pyrrolidine-dithio-carbamate ammonium (PDTC) on high-phosphate-induced vascular calcification in uremic rats.Methods Eight-week-old SD rats were pair-fed with standard chow containing 1.2％ calcium and 0.6％ phosphorus for the control group (n=8) or 0.75％ adenine,1.2％ calcium,and 1％ phosphorus for the chronic renal failure(CRF) group (n=8) or PDTC group (intraperitoneal injection,100 mg · kg-1 · d-1,n=8) for 8 weeks.The abdominal aortas were excised for Western blotting and immunostaining assay of NF-κB p65,osteopontin (OPN) and core binding factor α1(Cbfα1) protein.Results Serum urea nitrogen,creatinine,inorganic phosphate,calcium-phosphorus product increased significantly in CRF group and PDTC group after 4 weeks and 8 weeks (all P ＜ 0.01),although no differences were found between the latter two groups.After 8 weeks,aortic calcification was found in these two groups,immunostaining assay revealed OPN and Cbfα1 expressed in aortic intima,media and adventitia,and Western blotting analysis showed that total NF-κB p65,nuclear phosphorylated-p65 (p-p65),OPN and Cbfα1 expressions were significantly higher than those in control group (all P ＜ 0.01).The expression of total p65 and p-p65 was positively correlated with Cbfα1(r=0.707,P ＜ 0.01; r=0.507,P ＜ 0.01).Conclusion PDTC alleviates inorganic phosphate-induced aortic calcification significantly by inhibiting the nuclear translocation of NF-κB p65 and the expression of Cbfo1.
