诱导性自体干细胞移植后间质纤维化肾的结构与功能变化

Changes of structure and function in rabbit's kidney with interstitial fibrosis after induced autologous stem cell transplantation

目的观察诱导性自体干细胞经肾动脉移植对肾脏间质纤维化(UUO)模型兔肾功能及结构的影响。方法诱导兔成纤维细胞逆向分化为自体多能干细胞,经肾动脉移植到体内,分别于UUO损伤前和UUO损伤后第1、4、8w和移植后第1、4、8w于兔耳缘静脉采血,检测血清肌酐(Scr)和尿素氮(BUN),观察肾功能情况,并于UUO损伤后第16w和移植后第8w随机于模型组和移植组各取1只兔肾做病理切片,观察肾组织病理变化。结果UUO损伤后第4w,两组动物Scr、BUN开始逐渐升高(P<0.05或0.01);从诱导性自体干细胞移植后第4w起,移植组Scr、BUN水平逐渐低于模型组(P<0.05)。模型组可见肾小管数目减少、重度萎缩,萎缩的肾小管基底膜增厚、结构紊乱,肾小球囊腔扩张、囊腔内毛细血管球明显闭塞、呈缺血改变,肾间质弥漫性炎细胞浸润、重度纤维化,呈慢性病改变镜像;移植组可见肾小管中度萎缩,基底膜偏厚,小管多灶性扩张,肾小球囊腔扩张,肾间质散在炎细胞浸润、轻-中度纤维化改变。结论诱导性自体干细胞移植能降低肾脏UUO损伤后血清Scr和BUN水平,在一定程度上促进UUO损伤后的肾结构与功能修复。

Objective To observe the effects of the transplantation of induced autologous stem cell via renal artery on renal function and structure in rabbits with unilateral ureteral occlusion （UUO）. Methods The fibroblasts of rabbit were induced to differentiate reversely into autologous stem cells that were transplanted into rabbit;; body via renal artery subsequently. Before and 1,4,8 w after UUO as well as 1,4,8 w after transplantation,blood samples from the ear vein were used to measure serum creatinine （Ser） arat blood urea nitrogen （ BUN ） in order to observe rerial function. At 16 w after UUO and 8 w after transplantation ,two rabbit was randomly chosen from the model and transplantation group, respectively. Then kidney biopsy was done to observe the pathological changes in renal tissue. Results After UUO for 4 w,Scr anti BUN level in the two groups increased gradually （ P 〈 0.05 or 0.01 ）. However, after the transplantation of induced autologuus stem cell for 4 w, Scr and BUN level in the transplantation group were gradually lowered than those in the model group （P 〈 0.05）. Renal tubulars in the model group showed a lesser number, severe atrophy, basement membrane thickening and structural disorder;capsule of glomerulus expanded and its intracavitary capillaries showed isehemic changes and obvious occlusion; diffuse inflammation cell infiltration and severe fibrosis were seen in renal interstitium which demonstrated chronic changes. In transplantation group, moderate tubular atrophy, thick basement membrane, multifocal tubular expansion, glomerular cysts expansion could be seen; inflammatory, cells were scattered in renal interstitium showiug mild to moderate degree fibrosis. Conclusion The induced autologous stern cell transplantation can not only reduce Scr and BUN level,but also facilitate the repair of renal structure and function after UUO injury.