ILK在cGVHD狼疮样小鼠肾小管上皮细胞转分化中作用.docVIP

ILK在cGVHD狼疮样小鼠肾小管上皮细胞转分化中作用 　【摘要】 目的 观察整合素连接激酶（ILK）在慢性移植物抗宿主病(cGVHD)狼疮样小鼠肾脏中的表达，探讨其在狼疮肾炎肾小管上皮细胞转分化中的作用。方法 建立cGVHD狼疮样小鼠模型，将小鼠分成正常对照组(A组)、12周模型组(B组) 和16周模型组(C组)，每组6只。采用逆转录聚合酶链反应(RT-PCR)法、western blot、免疫组织化学法分别检测ILK 、E-钙粘蛋白和α-平滑肌肌动蛋白（α-SMA）mRNA和蛋白在肾组织中的表达。结果 RT-PCR和western blot方法分别检测到B、C两组小鼠肾组织ILK、α-SMA mRNA和蛋白表达较A组升高(P均＜0.01)， E-钙粘蛋白表达降低(P均＜0.01)。ILK蛋白和mRNA表达与α-SMA表达呈正相关（r分别为0.83，0.86，P均＜0.01），与E-钙粘蛋白表达呈负相关（r分别为-0.84，-0.89，P均＜0.01）。免疫组化结果表明，与A组相比，B、C两组小鼠肾小管及间质均可见ILK、α-SMA蛋白显著表达，而E-钙粘蛋白的表达显著减少。结论 cGVHD狼疮样小鼠肾组织中ILK蛋白及mRNA表达明显上调，可能通过介导肾小管上皮－间充质细胞转分化而参与了狼疮肾炎肾间质纤维化的进程。 【关键词】 移植物抗宿主病；狼疮肾炎；粘蛋白类；肾小管；小鼠；动物实验 　　Abstract: Objective To determine the expression of integrin-linked kinase (ILK) in renal tissue of mice with chronic graft versus host disease (cGVHD) lupus nephritis and its relationship with the epithelial-mesenchymal transition. Methods cGVHD lupus nephritis mice models were conducted. All the mice were divided into three groups: group A (control group, n=6), group B (12-week model group, n=6) and group C (16-week model group, n=6). The mice were killed twelve weeks later (group B) or sixteen weeks later (group C), respectively. The protein and mRNA expressions of ILK, alpha-SMA and E-Cadherin in kidney were detected by using immunohistochemistry, western blot and RT-PCR, respectively. Results The protein and mRNA expression of E-cadherin were significantly down-regulated (Plt;0.01) in group B and group C compared with group A, while expressions of ILK and alpha-SMA were up-regulated, respectively (Plt;0.01). The protein and mRNA expressions of ILK were positively correlated with alpha-SMA (r=0.83, and 0.86, all Plt;0.01), but adversely associated with E-cadherin (r=-0.84, and -0.89, all Plt;0.01). Conclusion The elevating expression of ILK may play an important role in the process of lupus nephritis through mediating the epithelial-mesenchymal transition. 　　Key words: graft versus host disease; lupus nephritis; mucins; kidney tubules; mice; animal experimentation