Therapeutic efficacy of bone marrow derived mesenchymal stromal cells versus losartan on adriamycin-induced renal cortical injury in adult albino rats
Therapeutic efficacy of bone marrow derived mesenchymal stromal cells versus losartan on adriamycin-induced renal cortical injury in adult albino rats
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DOI：
10.1016/j.jcyt.2016.05.004
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发表时间：
2016-08-01
期刊：
影响因子：
4.5
通讯作者：
Abd-El Fattah, Enas A.
中科院分区：
文献类型：
--
作者：
Anan, Hoda H.;Zidan, Rania A.;Abd-El Fattah, Enas A.
背景肾脏疾病是一个主要的健康问题。最近的研究报道了干细胞治疗在肾病动物模型中的疗效。工作的目的。本研究旨在探讨骨髓间充质干细胞（MSCs）与氯沙坦治疗阿霉素（ADR）所致肾脏病变的疗效。材料和方法。将35只成年雄性白化病大鼠分为4组。I组为对照组。第二组（阿霉素治疗组），腹腔注射阿霉素15 mg/kg，再分为Ⅱ a和Ⅱ b亚组，分别于注射阿霉素后1周和5周处死。第三组为阿霉素+氯沙坦治疗组，阿霉素注射后1周，5只大鼠口服氯沙坦10 mg/kg，每日1次，连续4周。第IV组为阿霉素+MSC治疗组）; 5只大鼠注射阿霉素作为第II组，然后在阿霉素注射后1周，在尾静脉中以每只大鼠1 × 106个细胞悬浮在0.5 mL磷酸盐缓冲盐水（PBS）中的剂量提供MSC。在干细胞注射后4周处死该组大鼠。测定血尿素氮和血清肌酐。取肾皮质标本进行光镜和电镜检查。光镜下行HE染色、PAS染色、Masson三色染色、增殖细胞核抗原（PCNA）和Caspase-3免疫组化染色。还进行了形态计量学和统计学分析。结果阿霉素治疗组肾功能下降，肾组织结构不同程度改变，细胞质空泡化，细胞核暗变，上皮衬里脱落。氯沙坦的管理部分改善ADR诱导的肾功能不全，而骨髓间充质干细胞表示更改善的作用，证明了结构和功能的恢复。结论骨髓间充质干细胞对ADR诱导的肾损伤具有相关的治疗潜力。MSCs可能通过减少caspase-3表达和增加增殖细胞核抗原染色来实现这一作用，从而影响肾脏的再生。
Background. Renal disease is a major health problem. Recent studies have reported the efficacy of stem cell therapy in nephropathy animal models. Aim of the work. This study was designed to investigate the therapeutic effectiveness of bone marrow-derived mesenchymal stromal cells (MSCs) versus losartan in the treatment of renal alterations induced by adriamycin (ADR). Materials and methods. Thirty-five adult male albino rats were divided into four groups. Group I was the control group. Group II (adriamycin-treated group), which included ten rats that were injected with a single dose of adriamycin (15 mg/kg) intraperitoneally, was subdivided into subgroup IIa and IIb and they were sacrificed 1 week and 5 weeks after adriamycin injection, respectively. Group III was the adriamycin + losartan-treated group and 1 week after adriamycin injection five rats received 10 mg/kg of losartan orally and daily for 4 weeks. Group IV was the adriamycin + MSC-treated group); five rats were injected with adriamycin as group II then supplied with MSCs at a dose of 1 x 10(6) cells suspended in 0.5 mL of phosphate-buffered saline (PBS) per rat in the tail vein 1 week after adriamycin injection. Rats of this group were sacrificed 4 weeks after the stem cell injection. Blood urea nitrogen and serum creatinine were measured. Samples from renal cortex were processed for light and electron microscope examination. As regards light microscope, sections were stained with hematoxylin and eosin (H-E), periodic acid-Schiff (PAS), masson trichrome, proliferating cell nuclear antigen (PCNA) and Caspase-3 immunohistochemical stains. Morphometrical and statistical analyses were also conducted. Results. Examination of adriamycin-treated group revealed deterioration of renal functions and various degrees of renal structural alterations as vacuolated cytoplasm, dark nuclei and detached epithelial lining. Administration of losartan partially improved ADR-induced kidney dysfunction, whereas MSCs denoted a more ameliorative role evidenced by structural and functional recovery. Conclusion. MSCs have a relevant therapeutic potential against ADR-induced renal damage. MSCs may accomplish this role by decreasing caspase-3 expression and increasing proliferating cell nuclear antigen staining which influence the regeneration of the kidney.