局灶节段性肾小球硬化患者足细胞钙神经蛋白的表达

Expression of calcineurin on podocytes of patients with focal segmental glomerulosclerosis

目的:观察成人局灶节段性肾小球硬化(focal segmental glomerulosclerosis,FSGS)患者足细胞钙神经蛋白的表达并探讨其意义。方法:选取临床表现为肾病综合征且经肾活检确诊的成人特发性FSGS63例,微小病变(minimal change disease,MCD)24例和肾移植供肾组织10例作为对照。免疫组化法检测肾组织钙神经蛋白A(CnA)异构体α、β、γ的表达。免疫荧光法行肾组织CnAα和synaptopodin双标记,并采用胶体金免疫电镜对肾小球CnAα的表达定位。两位病理医生分别盲法评分染色结果。结果:供肾组织肾小球CnAα、β、γ免疫组化染色均阴性,肾小管CnAα、β微弱表达,CnAγ阴性。26例FSGS患者肾小球足细胞CnAα表达上调,其阳性率为41.27%;而MCD患者肾小球CnAα阴性(P<0.01);两者肾小球CnAα、β、γ染色均阴性。足细胞CnAα阳性患者肾小管损伤指标尿视黄醇结合蛋白[20.91(0.17～54.37)mg/L]、血清肌酐[(128.18±56.58)μmol/L]高于阴性患者(P<0.05);两者间病理类型构成差异存在统计学意义(P<0.01);而年龄、性别、尿蛋白、尿N-乙酰-β-葡萄糖苷酶、血清白蛋白及胆固醇无统计学差异。塌陷型、细胞型、顶部型、门周型FSGS中足细胞CnAα阳性病例分别为5例(83.33%)、10例(66.67%)、8例(61.54%)、3例(20%),14例经典型FSGS患者均阴性。多因素Logistic回归分析示血清肌酐(OR4.855,P<0.01)、塌陷型(OR11.069,P<0.05)为FSGS患者足细胞CnAα过表达的主要相关因素。69.23%足细胞CnAα阳性患者肾小球syanptopodin表达减弱且不连续。结论:本研究首次发现部分FSGS患者足细胞上CnAα表达增强,这可能参与了FSGS的发病。FSGS与MCD患者足细胞CnAα的表达差异,提示二者发病机制不同。对临床怀疑FSGS而未见明确节段病变的患者,足细胞CnAα阳性有助于诊断。

Objective：To investigate whether calcineurin expression or not in podocytes of patients with focal segmental glomerulosclerosis （FSGS）. Methodology：The renal ealeineurin subunit A α,β,γ isoforms （ChAα,β,γ） were detected by immunohistochemistry in sixty-three adult nephrotie, biopsy-proven idopathic FSGS patients. Twenty-four cases with minimal change disease （ MCD）, and 10 donor renal grafts were regarded as control. CnAα and synaptopodin by immunofluorescence double staining was performed. The precise location of CnAα in glomeruli was confirmed by colloidal gold immunoeleetron microscopy. Immunostaining was scored by two pathologists in a double-blind manner. Results： Mild expression of CnAα and CnAα without CnAα, were found in renal tubules from donor renal grafts, while calcineurin wasn＇ t observed in glomeruli. CnAα expression was up-regulated in podocytes in cases with FSGS, however, CnAα and CnAα were negative. CnAα expression in podocytes increased in 26 （41.27%） FSGS cases, while all MCD were negative （P〈 0. 01 ）. Serum creatinine, urinary rentiol binding protein, pathological variants were significant different between podocyte CnAα posivtie and negative FSGS cases （ P 〈 0.05 ）. Podocyte CnAot posivte eases in Collapsing, Celluar, Tip, Hillar variant were 5 （83.33%）, 10 （66. 67% ）, 8 （61.54%） and 3 （20%）, respectively, but none in NOS（P 〈0. 01 ）. Serum ereatinine （ OR 4. 855, P 〈 0.01 ） , collapsing variant （ OR 11. 069, P 〈 0. 05 ） were critical factors for CnAαoverex-pression in podocytes of FSGS by Logistic regression. Synaptopodin was decreased and discontinued in 69. 23% cases with podocyte CnAα overexpression. Conclusion： We demonstrated that CnAα expresssion was upregulated in podocytes of some adult idopathic FSGS, which may be involved in the aggressive course. Differential expression of CnAα in podocytes suggests different pathogenic mechanism among FSGS variants and MCD. Detection of CnAα in podocytes is useful in distinction of FSGS versus MCD in renal biopsies without defining lesions.