CAJ | 학술논문

目的：观察骨髓间充质干细胞对阿霉素肾病大鼠的治疗作用及黏着斑激酶（FAK）的影响。方法建立阿霉素肾病大鼠模型，分别以干细胞与波尼松对照治疗，测定24 h尿蛋白，电镜观察肾组织结构，实时荧光定量PCR检测Nephrin、Desmin、FAK表达水平的变化，Western blot检测肾组织FAK蛋白及磷酸化，免疫组织化学方法检测Nephrin表达水平。结果（1）模型组大鼠均出现大量蛋白尿及足细胞足突广泛融合，骨髓间充质干细胞治疗组较模型组有改善。（2）与正常组比较，模型组Nephrin表达减少（P＜0.05），Desmin mRNA表达增多（P＜0.05），FAK mRNA表达升高（P＜0.01）；与模型组比较，各治疗组Nephrin表达水平增多（P＜0.05），Desmin mRNA表达水平减少（P＜0.05），FAK mRNA表达减少（P＜0.01）。（3）模型、各治疗组 Nephrin 蛋白表达水平低于正常组（P＜0.05），各治疗组 Nehprin蛋白表达水平较模型组有所增高（P＜0.05）。（4）模型组FAK总蛋白及磷酸化蛋白增高（P＜0.01），各治疗组FAK总蛋白及磷酸化蛋白较模型组降低，P＜0.05。结论骨髓间充质干细胞移植能抑制FAK活化，减轻蛋白尿，增加阿霉素肾病大鼠肾组织Nephrin表达水平，同时降低Desmin mRNA表达水平，对肾小球损伤起保护作用。
목적：관찰골수간충질간세포대아매소신병대서적치료작용급점착반격매（FAK）적영향。방법건립아매소신병대서모형，분별이간세포여파니송대조치료，측정24 h뇨단백，전경관찰신조직결구，실시형광정량PCR검측Nephrin、Desmin、FAK표체수평적변화，Western blot검측신조직FAK단백급린산화，면역조직화학방법검측Nephrin표체수평。결과（1）모형조대서균출현대량단백뇨급족세포족돌엄범융합，골수간충질간세포치료조교모형조유개선。（2）여정상조비교，모형조Nephrin표체감소（P＜0.05），Desmin mRNA표체증다（P＜0.05），FAK mRNA표체승고（P＜0.01）；여모형조비교，각치료조Nephrin표체수평증다（P＜0.05），Desmin mRNA표체수평감소（P＜0.05），FAK mRNA표체감소（P＜0.01）。（3）모형、각치료조 Nephrin 단백표체수평저우정상조（P＜0.05），각치료조 Nehprin단백표체수평교모형조유소증고（P＜0.05）。（4）모형조FAK총단백급린산화단백증고（P＜0.01），각치료조FAK총단백급린산화단백교모형조강저，P＜0.05。결론골수간충질간세포이식능억제FAK활화，감경단백뇨，증가아매소신병대서신조직Nephrin표체수평，동시강저Desmin mRNA표체수평，대신소구손상기보호작용。
Objective To investigate the repair effects of bone marrow mesenchymal stem cells (BMSCs) on adriamycin-induced nephritic rats and effects on FAK. Methods The rats models were induced by adriamycin to cause nephritic syndrome. Then, the rats were divided into four groups. The first group was the model without any treatment. The second group were treated with BMSCs. The third group were treated with prednisone. And the forth group were treated with BMSCs and prednisone. The quantitation of proteinuria was tested respectively. Histology of kidney was tested by transmission electron microscope. The expression levels of Nephrin, podocin and Desmin mRNA were tested by RT-PCR. The Nephrin protein levels were tested by immunohistochemistry. The expression level of FAK and phosphorylated FAK-Tyr397 were detected by western blot. Results (1) Compared with normal group, rats in model group developed massive Proteinuria with foot process fusion, while in BMSCs group were significantly ameliorated. (2)Nephrin mRNA expression in model group were lower than normal after adriamycin injection (P<0.05), while Desmin and FAK mRNA expression in model group were higher than normal group (P<0.05);Nephrin mRNA expression in treatment groups were lower than model group 5 weeks after adriamycin injection (P<0.05), while Desmin and FAK mRNA expression in treatment groups were lower than model group (P<0.05). (3)Nephrin protein expression in model group and the treatment groups were lower than normal group (P<0.05);Nephrin expression in treatment groups were higher than model group three weeks after adriamycin injection (P<0.05). (4)FAK total protein and phosphorylated proteins in model group higher than normal group (P<0.01). The protein level of treatment groups lower than model group (P<0.05). Conclusion Prednisone and BMSCs play a protective effect in ardriamycin-induced nephrotic rats via the inhibition of FAK and by altering the expression and distribution of Nephrin and moderating the expression of Desmin. BMSCs play a protective effect in ardriamycin-induced nephrotic rats.