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纸质出版:2007
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赵洪雯,余荣杰,刘宏,彭侃夫,吴雄飞.内皮祖细胞移植对延缓大鼠进展性局灶节段性肾小球硬化的实验研究[J].陆军军医大学学报(原第三军医大学学报),2007,29(21):2044-2048.
ZHAO Hong-wen,YU Rong-jie,LIU Hong,PENG Kan-fu,WU Xiong-fei.Endothelial progenitor cells transplantation ameliorates the progression of progressive focal segmental glomerular sclerosis[J].J Amry Med Univ (J Third Mil Med Univ),2007,29(21):2044-2048.
赵洪雯,余荣杰,刘宏,彭侃夫,吴雄飞.内皮祖细胞移植对延缓大鼠进展性局灶节段性肾小球硬化的实验研究[J].陆军军医大学学报(原第三军医大学学报),2007,29(21):2044-2048. DOI:
ZHAO Hong-wen,YU Rong-jie,LIU Hong,PENG Kan-fu,WU Xiong-fei.Endothelial progenitor cells transplantation ameliorates the progression of progressive focal segmental glomerular sclerosis[J].J Amry Med Univ (J Third Mil Med Univ),2007,29(21):2044-2048. DOI:
目的 骨髓来源的内皮祖细胞(endothelial progenitor cell,EPC)对阿霉素诱导的局灶节段性肾小球硬化模型进行干预,研究EPC的治疗作用。 方法 雄性大鼠骨髓的单个核细胞贴壁法培养6 d,经鉴定为EPC。雌性SD大鼠分为正常对照组、阿霉素肾病组和EPC移植组。肾病组、EPC组单肾切除,术后1周和2周分别尾静脉注射阿霉素,对照组假手术并在相同时间注射生理盐水。EPC组于第二次注射后1周,5 Gy X线全身照射后静脉移植1×10
6
的EPCs,对照组和肾病组仅行同等剂量的照射和生理盐水注射。在切肾前(0周)和切肾后的第4(即EPC移植后1周)、8、12、16周测大鼠体重、尿蛋白定量,眼球取血测血清肌酐(Scr)、白蛋白(ALB),原位杂交观察肾组织中Y染色体阳性细胞整合情况;观察肾脏超微结构和组织学变化,图像分析计算肾小球硬化指数、肾小球毛细血管管腔开放程度及毛细血管襻截面积。 结果 第4周和16周,肾组织中均可见Y染色体的阳性表达,主要位于肾小球和肾小管上皮细胞。16周时肾病组肾小球轻度至中度系膜细胞增生,基质中度至重度增生并呈弥漫性分布,肾小球节段性或球性硬化;EPC组部分肾小球系膜细胞及系膜基质呈局灶性轻度增生,硬化的肾小球数量少,间质纤维组织较肾病组轻;电镜结果显示EPC组病变较肾病组轻微,足细胞修复出现早;图像分析显示,肾小球硬化指数肾病组显著高于EPC组,毛细血管腔开放程度与毛细血管襻截面积EPC组显著高于肾病组,但仍低于对照组。 结论 EPC移植可以减轻肾脏病理损害,具有延缓阿霉素诱导的肾小球硬化的作用。
Objective To investigate the therapeutic effect of endothelial progenitor cells (EPCs) in ameliorating rat progressive focal segmental glomerular sclerosis (FSGS) model induced by adriamycin. Methods Bone marrow mononuclear cells from male SD rats
after cultured by adherence method
were identified as EPCs. Female SD rats were
divided into normal control group
adriamycin induced renal disease (ADR) group
EPCs transplantation group. ADR group and EPCs group underwent unilateral nephrectomy and received 5
3 mg/kg of adriamycin via tail vein 1 week and 2 weeks after operation
while the control group underwent sham operation and received 0.9% sodium chloride solution of equal volume. The whole body irradiation by 5 Gy X ray was done 1 week after the 2
nd
injection of adriamycin
then immediately 1×10
6
EPCs were transplanted via tail vein. The rats in control group and ADR group were only injected with 0.9% sodium chloride solution after whole body irradiation. The body weight and urine protein were measured before operation (0 week) and 4 (1 week after EPCs transplantation)
8
12 and 16 weeks after nephrectomy. Y chromatosome incorporation was detected with in situ hybridization at the 4
th
and 16
th
week. The histological and ultrastructural changes of kidney were evaluated at the 16
th
week. Results At the 4
th
and 16
th
weeks
Y chromatosome positive cells could be found incorporation in the area of glomerular and tubular epithelial cells. Since the 4
th
week
the weight of rats in both ADR group and EPC group became significantly less than that in control group and since the 8th week that in ADR group became less than that in EPC group (P0.05). The proteinuria and Scr were more severe in ADR group than that in EPC group and control group. In ADR group
mesangial proliferation and the tubulointerstitial fibrosis were more remarkable than that in EPC group and control group. The results of electron microscope showed that the lesions in podocytes and mesangial cells in ADR group were more severe than that of in EPC group at the 16
th
week. The image analysis showed that the index of glomerular sclerosis in ADR group and EPC group was significantly higher than that in control group
but was much better in EPC group than that in ADR group;
The opening degree of glomerular capillary cavity in EPC group was significantly higher than that of in ADR group
and so did the capillary sectional area. Conclusion EPCs transplantation can ameliorate renal damages and may delay the progression of glomerular sclerosis and tubulointerstial fibrosis induced by adriamycin.
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