层粘连蛋白α2亚链在膜性肾病肾小球基膜的异常分布

Abnormal distribution of laminin α2 chain in glomerular basement membrane in membranous nephropathy

目的观察Ⅳ型胶原和层粘连蛋白(laminin)亚链在膜性肾病(membranous nephropathy,MN)肾小球基膜(glomerular basement membrane,GBM)中的异常分布。方法收集52例MN肾组织,按照Ehrenreich和Churg提出的基于电镜形态特征的分期方法进行分期,同时收集10例微小病变肾组织作为正常GBM的对照。采用间接免疫荧光法检测不同分期MN肾组织GBM正常存在的代表性α5(Ⅳ)链及lamininα5、β2链的分布形态,以及可能异常存在的laminin α2、β1链的表达。结果在微小病变肾组织中α5(Ⅳ)链、lamininα5和β2链均沿GBM呈连续线状阳性;laminin α2、β1链在GBM中无表达。在Ⅰ期MN肾组织中α5(Ⅳ)链、lamininα5和β2链均呈连续线状表达。Ⅱ期MN肾组织中α5(Ⅳ)链在连续线状表达基础上形成大量钉突;lamininα5、β2链表达不规则增多,节段在连续线状表达基础上形成钉突。在Ⅲ期MN肾组织中α5(Ⅳ)链表达不规则增多,节段双轨状表达;lamininα5、β2链表达不规则增多,节段双轨、链环状表达。laminin α2链在Ⅰ期MN肾组织GBM未见明显阳性表达;在Ⅱ期和Ⅲ期MN肾组织GBM呈颗粒状阳性。lamininβ1链在各期MN肾组织GBM均未见明显阳性表达。结论MN患者GBM增厚不仅源自GBM固有Ⅳ型胶原亚链和laminin同种型的表达增多,还有正常仅表达于肾小球系膜区的laminin α2链的参与。

Purpose To study the abnormal distribution of type IV collagen and laminin chains in glomerular basement membrane （GBM） in membranous nephropathy （MN）. Methotis 52 cases of MN were collected and staged according to electron microscopic morphological characteristics, and 10 cases of kidney tissues of minimal change disease were used as normal GBM control. Distribution pattern of α5 （ IV ） chain, laminin α5 and β2 chains, and laminin α2 and β1 chains were detected using immunofluorescence method. Results In minimal change disease, α5 （ IV ） chain, laminin α5 and β2 chains all showed continuously linear positive expression along GBM, and laminin α2 and β1 chains were negatively expressed in GBM. In stage I MN, α5 （ IV ） chain, laminin α5 and β2 chains all showed continuous linear positive expression along GBM. In stage II MN, the expression of α5 （IV） chain was increased and showed abundant spikes on the basis of continuous linear positive staining along GBM, and the expression of laminin α5 and β2 chains was increased, and segmental spikes were seen on the basis of continuous linear positive staining along GBM. In stage III MN, the expression of α5 （ IV ） , laminin α5 and β2 chains was also enhanced and segmental double tracks were seen. The expression of laminin α2 chain was negative in GBM in stage I MN, but granular positive expression along GBM was seen in stage II and stage III MN. No positive expression of laminin β1 chain was seen in GBM in different stages in MN. Conclusion The GBM thickness in MN originates not only from intrinsic type IV collagen chains and laminin chains, but also from laminin α2 chain, which only exist in glomerulus mesangium in normal condition.