低氧诱导因子1α基因修饰脂肪干细胞修复小鼠急性肾损伤

Effect of adipose-derived stem cells modified with hypoxia-inducible factor-1 alpha gene on acute renal injury induced by cisplatin in mice

背景:干细胞移植为肾损伤的治疗提供了一个新的途径,治疗基因转染干细胞可增强对疾病的治疗效果。目的:探讨低氧诱导因子1α基因修饰的脂肪源性干细胞移植对急性肾损伤小鼠肾脏结构和功能的影响。方法:连续2d向BALB/C裸鼠腹腔注射10mg/kg顺铂诱导急性肾损伤小鼠模型。造模24h后经小鼠尾静脉注射含1×105个脂肪源性干细胞或转染低氧诱导因子1α的脂肪源性干细胞的细胞悬液,3d后留取小鼠血液及肾组织标本进行实验。以注射200μL生理盐水的急性肾损伤小鼠作为模型对照,以正常小鼠作为正常对照。结果与结论:脂肪源性干细胞干预后急性肾损伤小鼠血清肌酐、尿素氮水平降低,肾组织病理改变及肾小管上皮细胞的凋亡病变减轻,肾组织炎症因子RANTES、肿瘤坏死因子α表达降低,白细胞介素10表达升高;其中低氧诱导因子1α基因修饰的脂肪源性干细胞对肾组织细胞凋亡及炎症因子表达作用更明显。免疫荧光染色可见移植的脂肪源性干细胞的存活,但未见其向肾小管上皮细胞转化。结果表明脂肪源性干细胞移植可改善急性肾损伤小鼠的肾脏结构和功能,经低氧诱导因子1α基因修饰后的脂肪源性干细胞作用更显著。

BACKGROUND：Stem cells transplantation provides a new way for the treatment of renal injury.The effect could be enhanced by transfecting target gene before transplantation.OBJECTIVE：To explore the effect of adipose-derived mesenchymal stem cells transfected with hypoxia-inducible factor-1α gene on the structure and function of the kidney in mice with acute renal injury induced by cisplatin.METHODS：The cisplatin-induced acute renal injury mice model was established by intraperitoneal injecting with 10 mg/kg cisplatin for 2 days.At 24 hours after modeling,adipose-derived mesenchymal stem cells suspension containing 1×105 adipose-derived mesenchymal stem cells or hypoxia-inducible factor-1α was administrated through tail vein,after 3 days,the blood and kidney samples were detected.The acute renal injury mice injected with 200 μL normal saline were regarded as model controls,and the normal mice were as normal controls.RESULTS AND CONCLUSION：After adipose-derived mesenchymal stem cells intervention,the serum creatinine and blood urea nitrogen level were decreased,and the pathological changes of renal tissues and apoptosis lesions of renal tubular epithelial cells were decreased,as well as the expression of inflammatory cytokines RANTES of kidney tissue and tumor necrosis factor-α,while the expression of interleukin-10 was increased;the hypoxia-inducible factor-1α modified adipose-derived mesenchymal stem cells had a positive effect on renal cell apoptosis and expression of inflammatory cytokines.The immunofluorescence staining showed that a small quantity of green fluorescent protein from adipose-derived mesenchymal stem cells was present in renal tissue,but transformatation to the renal tubular epithelial cells was not observed.The results show that adipose-derived mesenchymal stem cells transplantation can improve the damage of the kidney structure and function in acute renal injury,and the adipose-derived mesenchymal stem cells transfected with hypoxia-inducible factor-1α are more effective in repairing acute renal injury.