膜性肾病患者足细胞钙神经蛋白表达的检测及其临床意义  

Detection of calcineurin expression in podocyte in patients with membranous nephropathy

作　　者：刘志红[1] 吴青[1] 汤曦[1] 张明超[1] 朱晓东[1] 左科[1] 郑春霞[1] 曾彩虹[1] 黎磊石[1] 

机构地区：[1]南京军区南京总医院解放军肾脏病研究所,南京210002

出　　处：《肾脏病与透析肾移植杂志》2010年第1期3-11,共9页Chinese Journal of Nephrology,Dialysis & Transplantation

摘　　要：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MN49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MN15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。Objective： The increased expression of calcineurin （CaN） in podocyte can directly damage the cytoskeleton structure, leading to podoeyte 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 caleinenrin 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 CnAct 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 lup

关 键 词：膜性肾病 钙神经蛋白 足细胞 

分 类 号：R692.3[医药卫生—泌尿科学]