骨髓间充质干细胞经肾动脉途径不同移植次数对大鼠阿霉素肾病的修复作用比较

目的 比较分析骨髓间充质干细胞(BMSC)经肾动脉途径单次或多次移植于阿霉素肾病大鼠后对其肾功能的改善作用.方法 以阿霉素经尾静脉输入构建大鼠慢性肾病模型32只,随机分为M0、M1、M2、M3组(4×n,n=8),另选8只为正常对照组(N组).以2×106个/ml、单次0.5 ml分别移植BMSC细胞0次(M0组)、1次(Ml组)、2次(M2组)、3次(M3组),不进行BMSC移植组别每次操作以L-DMEM培养基0.5 ml作为安慰剂对照,移植间隔为1周.移植前及末次移植后1、2周末检测大鼠血尿素氮、血肌酐、24 h尿蛋白、24 h尿微量蛋白,末次移植l周末制作病理片并于激光聚焦显微镜下观察大鼠肾脏病理和BMSC细胞在肾脏内分布情况.结果 M0、M1、M2、M3组在各观察点血尿素氮、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＜0.001),末次移植第1周末M2、M3组24 h尿蛋白总量、24 h尿微量蛋白明显低于M1组(P＜0.05),M2、M3组间差异无统计学意义(P=0.063).结论 BMSC经肾动脉途径移植2次治疗大鼠阿霉素肾病效果最宜.

Transplant of bone marrow mesenchymal stem cells via renal artery route in experimental rats with adriamycin-induced nephropathy: comparison of the repair effect on renal function between different times of transplant

Objective To compare the repair effect on renal function between different times of bone marrow mesenchymal stem cells (BMSCs) transplant via renal artery route in experimental rats with adriamycininduced nephropathy.Methods Adriamycin-induced nephropathy model was established in 32 rats through injection of adriamycin though the caudal vein.Based on the scheduled times of BMSCs transplant,the experimental rats were randomly and equally divided into M0 group (zero time),M1 group (one time),M2group (2 times) and M3 group (3 times) with 8 rats in each group.Other 8 SD rats were used as normal control group (N group).Single dose of 0.5 rnl BMSC suspension (2×106 cells/ml) was transplanted to the rats of M0 group (zero time),M1 group (one time),M2 group (2 times) and M3 group (3 times),for the rats of the groups not receiving BMSC transplant a single dose of 0.5 ml L-DMEM culture medium,used as a placebo,was adopted to replace BMSC suspension.The transplant interval was one week.Before transplant as well as one and two weeks after last time of transplant,the serum urea nitrogen,serum creatinine,24 h urine protein and 24 h urine microprotein were tested,and one week after last time of transplant pathological sections were made for laser focusing microscope examination to observe renal pathological changes and the distribution of BMSC cells in the kidney.Results The values of serum urea nitrogen,serum creatinine,24 h urine protein and 24 h urine microprotein determined at each observation time point in M0 group,M1 group,M2 group and M3 group were significantly higher than those in N group (P＜0.001).The values of 24 h urine protein and 24 h urine microprotein determined at one week after last time of transplant in M2 group and M3 group were strikingly lower than those in M1 group (P＜0.05),but these differences between M2 group and M3 group were not statistically significant (P=0.063).Conclusion For the treatment of adriamycin-induced nephropathy in experimental rats,two times of using BMSCs transplant via renal artery route can achieve optimal curative effect.