不同输注途径移植骨髓间充质干细胞对阿霉素肾病大鼠疗效初探

The Influence of Different Infusion Methods of Bone Marrow Mesenchymal Stem Cells in Adriamycin Nephropathy Rat Model

目的探索骨髓间充质干细胞(BMSCs)经不同输注方式移植入阿霉素慢性肾病大鼠体内对肾损伤的影响。方法SD大鼠左侧肾切除后以2.5 mg/kg剂量给大鼠尾静脉注射阿霉素,1次/周,连续2次,慢性肾病模型成功后,将成模大鼠36只随机均分为3组:阿霉素慢性肾病对照(ADR)组、干细胞经肾动脉移植(M-A)组、干细胞经外周静脉移植(M-V)组,另选12只正常大鼠设正常对照(N)组。BMSCs经体外培养后,以2×106个/mL经肾动脉注射到M-A组大鼠体内,2×106个/mL经尾静脉注射到M-V组大鼠体内,2周后再次同样方法注射等量BMSCs。检测移植当周、移植后1周、2周大鼠血尿素氮、血肌酐、24 h尿蛋白、24 h尿微量蛋白,末次注射干细胞后第1周于激光聚焦显微镜下观察大鼠肾脏病理和干细胞在肾脏内分布情况。结果M-A组、M-V组和ADR组在各观察时点血尿素氮、血肌酐、24 h尿蛋白总量、24 h尿微量蛋白均明显高于N组(P<0.01)。移植后1、2周M-A组的24 h尿微量蛋白低于ADR组(P<0.01),且M-A组的血肌酐较ADR组和M-V组均降低(P<0.01)。移植后1周,M-A组24 h尿蛋白、24 h尿微量蛋白明显低于M-V组(P<0.01);但2周时尿蛋白和微量蛋白与M-V组的差异无统计学意义。结论BMSCs移植可以改善阿霉素慢性肾病的肾损伤情况,在BMSCs移植后一段时间,BMSCs经肾动脉移植的效果优于经外周静脉移植。

Objective To investigate the effectiveness of bone marrow mesenchymal stem cell （MSC） and different transplantation methods of MSC on adriamycin （ADR） model of nephropathy in rats. Methods The ADR model of nephrop-athy was induced by left nephrectomy plus injection of ADR （2.5 mg/kg） in Sprague-Dawley （SD） rats, once a week for two weeks. The model rats with nephropathy were randomly divided into three groups： adriamycin nephropathic model control group （ADR, n=12）, MSCs transplantation through right renal artery group （M-A, n=12） and MSCs transplantation through peripheral veins group （M-V, n=12）. Another 12 SD rats were served as normal controls （N, n=12）. MSCs were cultured, transplanted via right renal artery （2×106/mL） to rats in M-A group, and were transplanted via peripheral veins 2×106/mL） to rats in M-V group. The same procedure was repeated in two weeks. The blood urea nitrogen, serum creatinine, 24 h urine protein and 24 h uromicroprotein were detected before transplantation and in one and two weeks after the second transplanta-tion. The renal morphology and labeled cells were examined in the kidney one week after the second transplantation. Results The values of blood urea nitrogen, serum creatinine, 24 h urine protein and 24 h uromicroprotein were significant-ly higher in M-A group, M-V group and ADR group than those of N group （P〈0.01）. The level of 24 h uromicroprotein was significantly lower before the second transplantation in M-A group than that of ADR group （P〈0.01）. The serum level of cre-atinine was significantly decreased in M-A group than that of ADR group and M-V group （P〈0.01）. The levels of 24 h urine protein and 24 h uromicroprotein were significantly lower after one week transplantation in M-A group than those of M-V group （P〈0.01）. The serum level of creatinine was significantly lower two weeks after the second transplantation in M-A group than that of ADR group and M-V group （P〈0.01）, but no significant differences in the levels of urine protein and uro-microprotein between M-A group and M-V group. Conclusion Transplantation of MSCs can alleviate renal damage of＆nbsp;chronic ADR-induced nephropathy, which is more effective in rats with MSCs transplantation via renal artery than that in rats with MSCs transplantation via peripheral vein.