肾脏病与透析肾移植杂志
腎髒病與透析腎移植雜誌
신장병여투석신이식잡지
CHINESE JOURNAL OF NEPHROLOGY,DIALYSIS & TRANSPLANTATION
2010年
1期
3-11
,共9页
刘志红%吴青%汤曦%张明超%朱晓东%左科%郑春霞%曾彩虹%黎磊石
劉誌紅%吳青%湯晞%張明超%硃曉東%左科%鄭春霞%曾綵虹%黎磊石
류지홍%오청%탕희%장명초%주효동%좌과%정춘하%증채홍%려뢰석
膜性肾病%钙神经蛋白%足细胞
膜性腎病%鈣神經蛋白%足細胞
막성신병%개신경단백%족세포
membranous nephropathy%calcineurin%podocyte
目的:足细胞上钙神经蛋白(calcineurin,CaN)的表达增加可直接破坏细胞骨架结构,导致足细胞损伤、蛋白尿产生.本研究通过观察膜性肾病(membranous nephropathy,MN)患者肾小球足细胞CaN的表达情况及其经钙神经蛋白抑制剂(calcineurin inhibitor,CNI)治疗后的变化,探讨其在指导治疗及发病机制研究中的意义.方法:选取经肾活检确诊的成人特发性MN 49例,利用免疫组化方法对肾组织钙神经蛋白A亚基α亚型(CnAα)及足细胞骨架蛋白synaptopodin进行检测,并对2例经他克莫司治疗蛋白尿完全缓解的病例,比较治疗前后肾组织CnAα的表达情况.此外,选取Ⅴ型狼疮性肾炎(LN)28例及乙肝相关性MN 15例,与特发性MN进行比较.结果:49例特发性MN患者中20例肾小球足细胞CnAα表达增加(40.8%),足细胞CnAα表达增加的同时伴synaptopodin表达减弱及分布异常.2例足细胞CnAα表达阳性的特发性MN患者采用他克莫司治疗获临床完全缓解后行重复肾活检,发现足细胞CnAα表达显著减弱,同时,synaptopodin表达强度明显增加,分布恢复正常.观察发现15例乙肝相关性MN患者中无一例足细胞CnAα阳性,而28例Ⅴ型LN中11例足细胞CnAα阳性(37.9%),其阳性率与特发性MN无明显差异.结论:本研究首次发现部分特发性MN患者存在足细胞CnAα表达增加及足细胞骨架结构的破坏.经CNI治疗蛋白尿完全缓解后,足细胞CnAα表达明显减少,同时synaptopodin的表达增加.部分Ⅴ型LN患者也存在足细胞CnAα表达的增加,其阳性率与特发性MN相比无明显差异,而乙肝相关性MN患者中无一例阳性.上述发现不仅为指导MN患者的个体化治疗开启了一个新的方向,也为进一步阐明特殊病因导致肾小球膜性病变及足细胞损伤的机制提供了新的途径.
目的:足細胞上鈣神經蛋白(calcineurin,CaN)的錶達增加可直接破壞細胞骨架結構,導緻足細胞損傷、蛋白尿產生.本研究通過觀察膜性腎病(membranous nephropathy,MN)患者腎小毬足細胞CaN的錶達情況及其經鈣神經蛋白抑製劑(calcineurin inhibitor,CNI)治療後的變化,探討其在指導治療及髮病機製研究中的意義.方法:選取經腎活檢確診的成人特髮性MN 49例,利用免疫組化方法對腎組織鈣神經蛋白A亞基α亞型(CnAα)及足細胞骨架蛋白synaptopodin進行檢測,併對2例經他剋莫司治療蛋白尿完全緩解的病例,比較治療前後腎組織CnAα的錶達情況.此外,選取Ⅴ型狼瘡性腎炎(LN)28例及乙肝相關性MN 15例,與特髮性MN進行比較.結果:49例特髮性MN患者中20例腎小毬足細胞CnAα錶達增加(40.8%),足細胞CnAα錶達增加的同時伴synaptopodin錶達減弱及分佈異常.2例足細胞CnAα錶達暘性的特髮性MN患者採用他剋莫司治療穫臨床完全緩解後行重複腎活檢,髮現足細胞CnAα錶達顯著減弱,同時,synaptopodin錶達彊度明顯增加,分佈恢複正常.觀察髮現15例乙肝相關性MN患者中無一例足細胞CnAα暘性,而28例Ⅴ型LN中11例足細胞CnAα暘性(37.9%),其暘性率與特髮性MN無明顯差異.結論:本研究首次髮現部分特髮性MN患者存在足細胞CnAα錶達增加及足細胞骨架結構的破壞.經CNI治療蛋白尿完全緩解後,足細胞CnAα錶達明顯減少,同時synaptopodin的錶達增加.部分Ⅴ型LN患者也存在足細胞CnAα錶達的增加,其暘性率與特髮性MN相比無明顯差異,而乙肝相關性MN患者中無一例暘性.上述髮現不僅為指導MN患者的箇體化治療開啟瞭一箇新的方嚮,也為進一步闡明特殊病因導緻腎小毬膜性病變及足細胞損傷的機製提供瞭新的途徑.
목적:족세포상개신경단백(calcineurin,CaN)적표체증가가직접파배세포골가결구,도치족세포손상、단백뇨산생.본연구통과관찰막성신병(membranous nephropathy,MN)환자신소구족세포CaN적표체정황급기경개신경단백억제제(calcineurin inhibitor,CNI)치료후적변화,탐토기재지도치료급발병궤제연구중적의의.방법:선취경신활검학진적성인특발성MN 49례,이용면역조화방법대신조직개신경단백A아기α아형(CnAα)급족세포골가단백synaptopodin진행검측,병대2례경타극막사치료단백뇨완전완해적병례,비교치료전후신조직CnAα적표체정황.차외,선취Ⅴ형랑창성신염(LN)28례급을간상관성MN 15례,여특발성MN진행비교.결과:49례특발성MN환자중20례신소구족세포CnAα표체증가(40.8%),족세포CnAα표체증가적동시반synaptopodin표체감약급분포이상.2례족세포CnAα표체양성적특발성MN환자채용타극막사치료획림상완전완해후행중복신활검,발현족세포CnAα표체현저감약,동시,synaptopodin표체강도명현증가,분포회복정상.관찰발현15례을간상관성MN환자중무일례족세포CnAα양성,이28례Ⅴ형LN중11례족세포CnAα양성(37.9%),기양성솔여특발성MN무명현차이.결론:본연구수차발현부분특발성MN환자존재족세포CnAα표체증가급족세포골가결구적파배.경CNI치료단백뇨완전완해후,족세포CnAα표체명현감소,동시synaptopodin적표체증가.부분Ⅴ형LN환자야존재족세포CnAα표체적증가,기양성솔여특발성MN상비무명현차이,이을간상관성MN환자중무일례양성.상술발현불부위지도MN환자적개체화치료개계료일개신적방향,야위진일보천명특수병인도치신소구막성병변급족세포손상적궤제제공료신적도경.
Objective:The increased expression of calcineurin(CaN)in podocyte can directly damage the cytoskeleton structure,leading to podocyte injury and proteinuria.It is interesting to know the expression of CaN in podocyte of patients with membranous nephropathy(MN)and its change after treatment with calcineurin inhibitor(CNI).Methodology:In the present study,the α isform of calcineurin A subunit(CnAα)expression in podocyte was detected by immunohistochemistry in 49 biopsy proven idiopathic MN,and the cytoskeleton protein,synaptopodin expression was observed at the same time in these patients.In addition,the alteration of podocyte CnAα expression after tacrolimus treatment in 2 cases of idiopathic MN were observed.Furthermore,28 cases of type Ⅴ lupus nephritis and 15 cases of hepatitis B virus associated MN were used as disease controls to clarify the specifity of the podocyte CnAα expression in idiopathic MN.Results:It was found that in 49 cases of idiopathic MN patients,20 patients showed increased expression of CnAα in podocyte(40.8%),accompanied by the decreased expression and discontinuous distribution of synaptopodin in the podocyte.Repeat renal biopsy revealed that after complete remission treated with tacrolimus,the CnAα expression significantly reduced,meanwhile the intensity of synaptopodin expression increased with normalized distribution in the podocyte.None of the hepatitis B virus associated MN patients had increased expression of CnAα in podocyte ,however,11 out of 28 cases of type Ⅴ lupus nephritis had increased expression of CnAα in podocyte(37.9%),the frequency is similar with idiopathic MN.Conclusion:Increased expression of CnAα in podocyte was present in part of patients with idiopathic MN,this change was accompanied by the podocyte cytoskeleton destruction.After complete remission treated with CNI,the podocyte CnAα expression decreased significantly,with normalized synaptopodin expression and distribution.The tpye Ⅴ lupus nephritis patients showed the similar frequency of increased expression of CnAα in podocyte with idiopathic MN,while none of the hepatitis B virus associated MN patients had increased CnAα expression.This result shed light on the individual therapy not only for idiopathic MN,but also for other podocyte disease.