腺病毒介导胶原蛋白Ⅳα5在X连锁Alport综合症动物模型肾脏表达的实验研究.pdfVIP

400 分子诊断与治疗杂志　2010 年 11 月第 2 卷第 6 期　J Mol Diagn Ther, November 2010, Vol. 2 No. 6 · · •论 著• 腺病毒介导胶原蛋白 IV α5 在 X 连锁 Alport 综合症 动物模型肾脏表达的实验研究 1 2 邹德芹 　徐向军 [ 摘　要 ] 目的　探讨在 X 染色体连锁 Alport 综合体（X-Linked Alport syndroms, XLAS ）狗模型 肾小球基底膜上外源性表达胶原蛋白 IV α5 的可行性。　方法　选择能够理想模拟人 XLAS 病例的 5~7 个月大 NAV 狗，在血肌酐正常和尿蛋白阴性条件下，在体封闭肾脏循环持续灌注重组人 COL4A5 cDNA 腺病毒载体 1 h，术后 4 周，灌注侧肾脏单克隆 IgG 行间接免疫荧光染色。　结果　α5 链在部分皮质肾 小球毛细血管袢上显著表达。　结论　本研究为进一步修复基底膜滤过屏障中 α3/ α4/ α5 三聚体网状结 构，基因治疗 XLAS 提供了重要的动物实验依据。 [ 关键词 ]　X 染色体连锁 Alport 综合症；COL4A5 ；狗；腺病毒；肾脏；灌注 Adenovirus-mediated expression of type IV collagen α 5 chain in the canine kidney with X-linked Alport syndrome 1 2 ZOU Deqin , XU Xiangjun (1.Division of Emergency, Changjiang Hospital, Hubei, Wuhan 430019, China; 2.Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm 17177, Sweden) [ABSTRACT] Objective　To explore the feasibility of expressing exogenous collagen α5(IV) chain in the GBM of canine kidney with X-linked Alport syndrome.　Methods　The full-length human COL4A5 cDNA was transferred into 5~7 months old canine kidney with XLAS in vivo, by which a surgical closed-circuit kidney perfusion was performed with recombinant adenoviruses for one hour. The operative kidney was labeled by monoclonal IgG in the method of indirect immunofluorescence after four weeks.　Results　There was positive result that α5 chains were strongly expressed in glomerular capillaries amongst partial renal cortex. 　Conclusion　It is an important advance concerning the potential recovery of α3/ α4/ α5 trimer and gene therapy of XLAS. [KEY WORDS]　XLAS; COL4A5 ; Canine; Adenovirus; Kidney; Perfusion Alport 综合症是一